Real-time surveillance of severe acute respiratory infections in Scottish hospitals: an electronic register-based approach, 2017-2022.

OBJECTIVES: The COVID-19 pandemic highlighted the importance of routine syndromic surveillance of respiratory infections, specifically new cases of severe acute respiratory infection (SARI). This surveillance often relies on questionnaires carried out by research nurses or transcriptions of doctor's notes, but existing, routinely collected electronic healthcare data sets are increasingly being used for such surveillance. We investigated how patient diagnosis codes, recorded within such data sets, could be used to capture SARI trends in Scotland. STUDY DESIGN: We conducted a retrospective observational study using electronic healthcare data sets between 2017 and 2022. METHODS: Sensitive, specific and timely case definition (CDs) based on patient diagnosis codes contained within national registers in Scotland were proposed to identify SARI cases. Representativeness and sensitivity analyses were performed to assess how well SARI cases captured by each definition matched trends in historic influenza and SARS-CoV-2 data. RESULTS: All CDs accurately captured the peaks seen in laboratory-confirmed positive influenza and SARS-CoV-2 data, although the completeness of patient diagnosis records was discovered to vary widely. The timely CD provided the earliest detection of changes in SARI activity, whilst the sensitive CD provided insight into the burden and severity of SARI infections. CONCLUSIONS: A universal SARI surveillance system has been developed and demonstrated to accurately capture seasonal SARI trends. It can be used as an indicator of emerging secondary care burden of emerging SARI outbreaks. The system further strengthens Scotland's existing strategies for respiratory surveillance, and the methods described here can be applied within any country with suitable electronic patient records.

Complex differences in infection rates between ethnic groups in Scotland: a retrospective, national census-linked cohort study of 1.65 million cases.

BACKGROUND: Ethnicity can influence susceptibility to infection, as COVID-19 has shown. Few countries have systematically investigated ethnic variations in infection. METHODS: We linked the Scotland 2001 Census, including ethnic group, to national databases of hospitalizations/deaths and serological diagnoses of bloodborne viruses for 2001-2013. We calculated age-adjusted rate ratios (RRs) in 12 ethnic groups for all infections combined, 15 infection categories, and human immunodeficiency virus (HIV), hepatitis B (HBV) and hepatitis C (HCV) viruses. RESULTS: We analysed over 1.65 million infection-related hospitalisations/deaths. Compared with White Scottish, RRs for all infections combined were 0.8 or lower for Other White British, Other White and Chinese males and females, and 1.2-1.4 for Pakistani and African males and females. Adjustment for socioeconomic status or birthplace had little effect. RRs for specific infection categories followed similar patterns with striking exceptions. For HIV, RRs were 136 in African females and 14 in males; for HBV, 125 in Chinese females and 59 in males, 55 in African females and 24 in males; and for HCV, 2.3-3.1 in Pakistanis and Africans. CONCLUSIONS: Ethnic differences were found in overall rates and many infection categories, suggesting multiple causative pathways. We recommend census linkage as a powerful method for studying the disproportionate impact of COVID-19.

National population prevalence of antibodies to SARS-CoV-2 in Scotland during the first and second waves of the COVID-19 pandemic.

OBJECTIVES: Studies that measure the prevalence of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ('seroprevalence') are essential to understand population exposure to SARS-CoV-2 among symptomatic and asymptomatic individuals. We aimed to measure seroprevalence in the Scottish population over the course of the COVID-19 pandemic - from before the first recorded case in Scotland through to the second pandemic wave. STUDY DESIGN: The study design of this study is serial cross sectional. METHODS: We tested 41,477 residual samples retrieved from primary and antenatal care settings across Scotland for SARS-CoV-2 antibodies over a 12-month period from December 2019-December 2020 (before rollout of COVID-19 vaccination). Five-weekly rolling seroprevalence estimates were adjusted for the sensitivity and specificity of the assays and weighted to reference populations. Temporal trends in seroprevalence estimates and weekly SARS-CoV-2 notifications were compared. RESULTS: Five-weekly rolling seroprevalence rates were 0% until the end of March, when they increased contemporaneously with the first pandemic wave. Seroprevalence rates remained stable through the summer (range: 3%-5%) during a period of social restrictions, after which they increased concurrently with the second wave, reaching 9.6% (95% confidence interval [CI]: 8.4%-10.8%) in the week beginning 28th December in 2020. Seroprevalence rates were lower in rural vs. urban areas (adjusted odds ratio [AOR]: 0.70, 95% CI: 0.61-0.79) and among individuals aged 20-39 years and 60 years and older (AOR: 0.74, 95% CI: 0.64-0.86; AOR: 0.80, 95% CI: 0.69-0.91, respectively) relative to those aged 0-19 years. CONCLUSIONS: After two waves of the COVID-19 pandemic, less than one in ten individuals in the Scottish population had antibodies to SARS-CoV-2. Seroprevalence may underestimate the true population exposure as a result of waning antibodies among individuals who were infected early in the first wave.

Enhanced surveillance of COVID-19 in Scotland: population-based seroprevalence surveillance for SARS-CoV-2 during the first wave of the epidemic.

OBJECTIVES: The impact of the COVID-19 pandemic in Scotland has been amongst the most severe in Europe. Serological surveillance is critical to determine the overall extent of infection across populations and to inform the public health response. This study aimed to estimate the proportion of people who have antibodies to SARS-CoV-2 ('seroprevalence') in the general population of Scotland and to see if this changes over time. STUDY DESIGN/METHODS: Between International Organization for Standardization (ISO) week 17 (i.e. week commencing 20th April) and ISO week 25 (week commencing 15 June), 4751 residual blood samples were obtained from regional biochemistry laboratories in six participating regional health authority areas covering approximately 75% of the Scottish population. Samples were tested for the presence of anti-SARS-CoV-2 IgG antibodies using the LIAISON®SARS-CoV-2 S1/S2 IgG assay (DiaSorin, Italy). Seroprevalence rates were adjusted for the sensitivity and specificity of the assay using Bayesian methods. RESULTS: The combined adjusted seroprevalence across the study period was 4.3% (95% confidence interval: 4.2%-4.5%). The proportion varied each week between 1.9% and 6.8% with no difference in antibody positivity by age, sex or geographical area. CONCLUSIONS: At the end of the first wave of the COVID-19 pandemic, only a small fraction of the Scottish population had antibodies to SARS-CoV-2. Control of COVID-19 requires the ability to detect asymptomatic and mild infections that would otherwise remain undetected through existing surveillance systems. This is important to determine the true number of infections within the general population which, in turn, can help to understand transmission, inform control measures and provide a denominator for the estimation of severity measures such as the proportion of infected people who have been hospitalised and/or have died.

Increased case-finding and uptake of direct-acting antiviral treatment essential for micro-elimination of hepatitis C among people living with HIV: a national record linkage study.

OBJECTIVES: Micro-elimination of hepatitis C virus (HCV) in people living with HIV (PLHIV) and co-infected with HCV has been proposed as a key contribution to the overall goal of HCV elimination. While other studies have examined micro-elimination in HIV-treated cohorts, few have considered HCV micro-elimination among those not treated for HIV or at a national level. METHODS: Through data linkage of national and sentinel surveillance data, we examined the extent of HCV testing, diagnosis and treatment among a cohort of PLHIV in Scotland identified through the national database of HIV-diagnosed individuals, up to the end of 2017. RESULTS: Of 5018 PLHIV, an estimated 797 (15%) had never been tested for HCV and 70 (9%) of these had undiagnosed chronic HCV. The odds of never having been tested for HCV were the highest in those not on HIV treatment [adjusted odds ratio (aOR) = 7.21, 95% confidence interval (CI): 5.15-10.10). Overall HCV antibody positivity was 11%, and it was at its highest among people who inject drugs (49%). Most of those with chronic HCV (91%) had attended an HCV treatment clinic but only half had been successfully treated (54% for those on HIV treatment, 12% for those not) by the end of 2017. The odds of never having been treated for HCV were the highest in those not on HIV treatment (aOR = 3.60, 95% CI: 1.59-8.15). CONCLUSIONS: Our data demonstrate that micro-elimination of HCV in PLHIV is achievable but progress will require increased effort to engage and treat those co-infected, including those not being treated for their HIV.

HPV vaccine uptake in men who have sex with men in Scotland.

Human papillomavirus (HPV) vaccines are currently utilised globally in national immunisation programmes. In July 2017, a national HPV vaccine programme for men who have sex with men (MSM) was initiated across Scotland with vaccine being offered in the sexual health clinic setting. During the first year of this targeted vaccination programme, there were 5905 individuals who received at least one dose of HPV vaccine, representing 63.7% of eligible MSM attendees in this period. Vaccine uptake was relatively stable across all age groups (range 49.8-55.5%). The vaccination programme appears to have dovetailed well with pre-existing sexual health services and appears to be popular with MSM attending the service. The MSM HPV vaccine programme is a robust adjunct to the national girls programme but gender-neutral immunisation will reduce stigma and inequality in HPV-driven disease.

Apnoeic oxygenation during intubation: a systematic review and meta-analysis.

Apnoeic oxygenation during intubation is used to prevent desaturation during intubation. The aim of this review was to assess whether apnoeic oxygenation during endotracheal intubation reduced the incidence of hypoxaemia. Five major databases were systematically searched for all relevant studies published up to May 2016. All study designs with a control group and a group receiving apnoeic oxygenation were included in this review. These studies were then assessed for level of evidence and risk of bias. The data were then analysed using a meta-analysis. Eleven studies (six high quality randomised controlled trials, four low quality level two studies and one low quality level three study) were found. In the meta-analysis there was strong evidence for benefit of apnoeic oxygenation in terms of improved SpO2 in elective surgical patients, obese patients and those undergoing emergency intubation without respiratory failure. However, no significant benefit was found in patients with respiratory failure. This is the first meta-analysis to be performed on apnoeic oxygenation during intubation. Apnoeic oxygenation provides significant benefit in terms of improving SpO2 for the majority of intubations, although there appears to be no benefit in patients whose indication for intubation is respiratory failure. Apnoeic oxygenation ought to be considered for integration into intubation protocols.

Fine and ultrafine particle exposures on 73 trips by car to 65 non-smoking restaurants in the San Francisco Bay Area.

A number of studies indicate cooking is a major source of exposure to particulate matter, but few studies have measured indoor air pollution in restaurants, where cooking predominates. We made 73 visits by car to 65 different non-smoking restaurants in 10 Northern California towns while carrying portable continuous monitors that unobtrusively measured ultrafine (down to 10 nm) and fine (PM2.5 ) particles to characterize indoor restaurant exposures, comparing them with exposures in the car. The mean ultrafine number concentrations in the restaurants on dinner visits averaging 1.4 h was 71 600 particles/cm3 , or 4.3 times the mean concentration on car trips, and 12.3 times the mean background concentration in the residence. Restaurants that cooked dinner in the same room as the patrons had higher ultrafine concentrations than restaurants with separate kitchens. Restaurant PM2.5 mass concentrations averaged 36.3 µg/m3 , ranging from 1.5 to 454 µg/m3 , but were relatively low on most visits: 43% of the indoor means were below 10 µg/m3 and 66% were below 20 µg/m3 , with 5.5% above 100 µg/m3 . Exposure to fine and ultrafine particles when visiting a restaurant exceeded the exposure a person received while traveling by car to and from the restaurant.

Risk factors for TB and HIV coinfection in Scotland, 2001 to 2010.

The number of patients with tuberculosis (TB) increased steadily in Scotland between 2005 and 2010. Human immunodeficiency virus (HIV) infection has been a contributory factor to increases in TB in a number of comparable industrialised countries. This study investigated the extent of, and risk factors for, TB and HIV coinfection in Scotland from 2001 to 2010. Patients with TB in the national TB database were linked to those in the national HIV database using probabilistic data linkage. Patient records were anonymised to maintain confidentiality. From 2001 to 2010, 106/4, 097 (2.6%, 95% CI: 2.1 to 3.1) TB patients matched with HIV patients, equating to a 10-year incidence of 2.1 cases per million population. Patients with both TB and HIV were more often born outside the United Kingdom,were of black African ethnicity, had refugee status and had extra-thoracic lymph node involvement or cryptic/disseminated TB disease. Individuals with TB and HIV coinfection were younger and symptomatic for a shorter time before their diagnosis of TB, compared with TB patients without HIV. TB and HIV coinfection was relatively uncommon in Scotland in the study period. Clinicians should recognise the potential for HIV infection among TB patients and the importance of offering an HIV test to all TB patients.

Ultrafine particles from electric appliances and cooking pans: experiments suggesting desorption/nucleation of sorbed organics as the primary source.

Ultrafine particles are observed when metal surfaces, such as heating elements in electric appliances, or even empty cooking pans, are heated. The source of the particles has not been identified. We present evidence that particles >10 nm are not emitted directly from the heating elements or the metal surfaces. Using repeated heating of an electric burner, several types of cooking pans, and a steam iron, the increase in the number of particles (>10 nm) can be reduced to 0. After the devices are exposed to indoor air for several hours or days, subsequent heating results in renewed particle production, suggesting that organic matter has sorbed on their surfaces. Also, after a pan has been heated to the point that no increase in particles is observed, washing with detergent results in copious production of particles the next time the pan is heated. These observations suggest that detergent residue and organics sorbed from indoor air are the sources of the particles. We hypothesize that organic compounds are thermally desorbed from the hot surface as gaseous molecules; as they diffuse from the hot air near the pan into cooler air, selected compounds exceed their saturation concentration and nucleation occurs.

British Association for Sexual Health and HIV Scottish investigation 2010-2011: reasons for non-attendance in individuals lost to follow-up for HIV care for more than 12 months in Scotland.

As of 31 March 2011, 6696 HIV diagnoses had ever been reported in Scotland; of these, 1791 individuals had died, 3339 were attending specialist services, but the remainder had defaulted from specialist care; an investigation into their reasons for non-attendance, and the efforts of services to re-engage, was undertaken by British Association for Sexual Health and HIV Scottish branch using a web-based survey questionnaire. Twelve of the 13 Scottish HIV services returned information for 424 of 579 eligible cases; 112 of these 424 individuals were identified as genuine non-attendees. Findings indicate that the epidemiology of these non-attendees is similar to that of the whole Scottish HIV cohort. Three-quarters of individuals failed to attend a booked appointment following their last known attendance and very few attempts to contact non-attending individuals were successful. This survey has refocused attention on those lost to follow-up, while quality of the national data-set has improved, providing a clearer epidemiological picture of people living with HIV in Scotland.

Heterosexual transmission of infectious syphilis in central Scotland, 2009.

A local outbreak of infectious syphilis among heterosexual men and women was noted among residents of a National Health Services board in central Scotland in 2009. This is the first, and remains the only, such outbreak in Scotland reporting transmission in the heterosexual population. It was characterized by the young age of those infected. This highlights the need for increasing knowledge and awareness of syphilis infection among this group.

Molecular epidemiology of syphilis in Scotland.

OBJECTIVE: To examine the molecular epidemiology of syphilis in Scotland. METHODS: Ulcer specimens were collected from 85 patients with infectious syphilis. Typing of Treponema pallidum was performed using a method that examines variation in two loci; the number of 60-basepair repeats within the arp gene and sequence variation in the tpr genes. RESULTS: Patients were predominately white men who have sex with men (MSM). Treponemal DNA was detected in 75 specimens and a total of six subtypes were identified from 58 typeable specimens (77%). The most common subtypes were 14d (44/58, 76%), followed by 14e (7/58, 12%), 14j (3/58, 5%), 14b (2/58, 3%), 14p and 14k (1/58, 2%). CONCLUSIONS: This study shows that subtype 14d is the predominant subtype circulating in Scotland and there is a surprising level of genetic diversity within the Scottish MSM community.

What is the excess risk of infertility in women after genital chlamydia infection? A systematic review of the evidence.

OBJECTIVE: To summarise evidence on the attributable risk of infertility after chlamydial infection in women. METHODS: Twelve databases were searched, limited to peer-reviewed literature published from January 1970 to September 2007. Conference abstracts and reference lists from reviews published since 2000 and from key articles were hand-searched. Studies were selected for review if they met the following criteria: (1) the study population comprised women of child-bearing age (defined as 15-45 years) and incorporated a comparison group of women documented as "chlamydia negative"; (2) the study outcomes included either infertility or successful pregnancy; and (3) the study design was one of the following: cohort, randomised controlled trial, "before and after" study, screening trial and systematic review. Studies were excluded if they described genital infections that either did not include Chlamydia trachomatis or described genital chlamydial co-infection, in which no data were available for C trachomatis infection alone. RESULTS: 3349 studies were identified by the search. One study satisfied the inclusion criteria, a longitudinal investigation measuring pregnancy rates in adolescent women with and without current chlamydial infection at baseline. That study reported no significant difference in subsequent pregnancy rates; however, it had serious methodological limitations, which restricted its conclusions. CONCLUSIONS: This systematic review demonstrates the absence of valid evidence on the attributable risk of post-infective tubal factor infertility after genital chlamydial infection. The findings contribute empirical data to the growing debate surrounding previous assumptions about the natural history of chlamydial infection in women.

Analysis of indoor particle size distributions in an occupied townhouse using positive matrix factorization.

UNLABELLED: From late 1999 to early March 2000, measurements of particle number (particles 0.01-20 microm in aerodynamic diameter) concentrations were made inside of a townhouse occupied by two non-smoking adults and located in Reston, VA (approximately 25 miles northwest of Washington, DC). The particle size measurements were made using an SMPS and an APS as well as a Climet optical scattering instrument. In this study, positive matrix factorization (PMF) was used to study the indoor particle size distributions. The size distributions or profiles obtained were identified by relating the obtained source contributions to the source information provided by the occupants. Nine particle sources were identified, including two sources associated with gas burner use: boiling water and frying tortillas. Boiling water for tea or coffee was found to be associated only with the smallest particles, with a number mode close to the detection limit of the SMPS (i.e., 0.01 microm). Frying tortillas produced particles with a number mode at about 0.09 microm while broiling fish produced particles with a number mode at about 0.05 microm. A citronella candle was often burned during the study period, and this practice was found to produce a 0.2-microm modal number distribution. Other indoor particle sources identified included sweeping/vacuuming (volume mode at 2 microm); use of the electric toaster oven (number mode at 0.03 microm); and pouring of kitty litter (volume mode over 10 microm). Two outdoor sources were also resolved: traffic (number mode at about 0.15 microm) and wood smoke (major number mode at about 0.07 microm). The volume distributions showed presence of coarse particles in most of the resolved indoor sources probably caused by personal cloud emissions as the residents performed the various indoor activities. PRACTICAL IMPLICATIONS: This study has shown that continuous measurements of indoor particle number and volume concentrations together with records of personal activities are useful for indoor source apportionment models. Each of the particle sources identified in this study produces distinct size distributions that may be useful in studying the mortality and morbidity effects of airborne particulate matter because they will have different penetrability and deposition patterns.

Costs of running a universal adolescent hepatitis B vaccination programme.

In the first UK study to examine feasibility and acceptability of universal adolescent hepatitis B vaccination, the costs associated with the administration and uptake (80.2 and 89.3% for three doses and at least two doses, respectively), of a three-dose regimen in pupils in Glasgow schools (2001/2002) were measured. These data were used to estimate the economic outlay for the delivery of a routine, ongoing three-dose and two-dose hepatitis B vaccine programme in schools. Vaccine, accounting for almost 70% of the overall costs, was the largest cost item for both the pilot and routine programmes, using either regimen. However, the ongoing, two-dose regimen was the cheapest option in this analysis, irrespective of vaccine price. Cost data from this study may be useful for other countries wishing to implement a similar programme.

Determinants of universal adolescent hepatitis B vaccine uptake.

The UK is currently considering the introduction of universal hepatitis B vaccination. This study of determinants of vaccine uptake among school based adolescents shows that living in areas of high deprivation, commonly associated with injecting drug risk behaviours, was the most important factor, with statistically significant lower odds of receiving three doses. This was less pronounced for receipt of two doses. Thus, there are implications for future policy; if universal vaccination is approved, a licensed two dose schedule would be most appropriate in this setting.

Continuous measurements of air change rates in an occupied house for 1 year: the effect of temperature, wind, fans, and windows.

A year-long investigation of air change rates in an occupied house was undertaken to establish the effects of temperature, wind velocity, use of exhaust fans, and window-opening behavior. Air change rates were calculated by periodically injecting a tracer gas (SF(6)) into the return air duct and measuring the concentration in 10 indoor locations sequentially every minute by a gas chromatograph equipped with an electron capture detector. Temperatures were also measured outdoors and in the 10 indoor locations. Relative humidity (RH) was measured outdoors and in five indoor locations every 5 min. Wind speed and direction in the horizontal plane were measured using a portable meteorological station mounted on the rooftop. Use of the thermostat-controlled attic fan was recorded automatically. Indoor temperatures increased from 21 degrees C in winter to 27 degrees C in summer. Indoor RH increased from 20% to 70% in the same time period. Windows were open only a few percent of the time in winter but more than half the time in summer. About 4600 hour-long average air change rates were calculated from the measured tracer gas decay rates. The mean (SD) rate was 0.65 (0.56) h(-1). Tracer gas decay rates in different rooms were very similar, ranging only from 0.62 to 0.67 h(-1), suggesting that conditions were well mixed throughout the year. The strongest influence on air change rates was opening windows, which could increase the rate to as much as 2 h(-1) for extended periods, and up to 3 h(-1) for short periods of a few hours. The use of the attic fan also increased air change rates by amounts up to 1 h(-1). Use of the furnace fan had no effect on air change rates. Although a clear effect of indoor-outdoor temperature difference could be discerned, its magnitude was relatively small, with a very large temperature difference of 30 degrees C (54 degrees F) accounting for an increase in the air change rate of about 0.6 h(-1). Wind speed and direction were found to have very little influence on air change rates at this house.

Universal hepatitis B vaccination of UK adolescents: a feasibility and acceptability study.

The feasibility of introducing universal hepatitis B immunisation was assessed by offering the vaccine to all 11-12 year old pupils in Greater Glasgow (approximately 10,800). Consent was received from 92% of the school roll, and 91.3%, 89.2% and 80.3% received at least 1, at least 2, and 3 doses respectively. The findings of this study constitute key evidence for the ongoing debate in the UK on hepatitis B vaccination.

Equilibrium folding of dimeric class mu glutathione transferases involves a stable monomeric intermediate.

The conformational stabilities of two homodimeric class mu glutathione transferases (GSTM1-1 and GSTM2-2) were studied by urea- and guanidinium chloride-induced denaturation. Unfolding is reversible and structural changes were followed with far-ultraviolet circular dichroism, tryptophan fluorescence, enzyme activity, chemical cross-linking, and size-exclusion chromatography. Disruption of secondary structure occurs as a monophasic transition and is independent of protein concentration. Changes in tertiary structure occur as two transitions; the first is protein concentration dependent, while the second is weakly dependent (GSTM1-1) or independent (GSTM2-2). The second transition corresponds with the secondary structure transition. Loss in catalytic activity occurs as two transitions for GSTM1-1 and as one transition for GSTM2-2. These transitions are dependent upon protein concentration. The first deactivation transition coincides with the first tertiary structure transition. Dimer dissociation occurs prior to disruption of secondary structure. The data suggest that the equilibrium unfolding/refolding of the class mu glutathione transferases M1-1 and M2-2 proceed via a three-state process: N(2) <--> 2I <--> 2U. Although GSTM1-1 and GSTM2-2 are homologous (78% identity/94% homology), their N(2) tertiary structures are not identical. Dissociation of the GSTM1-1 dimer to structured monomers (I) occurs at lower denaturant concentrations than for GSTM2-2. The monomeric intermediate for GSTM1-1 is, however, more stable than the intermediate for GSTM2-2. The intermediates are catalytically inactive and display nativelike secondary structure. Guanidinium chloride-induced denaturation yields monomeric intermediates, which have a more loosely packed tertiary structure displaying enhanced solvent exposure of its tryptophans and enhanced ANS binding. The three-state model for the class mu enzymes is in contrast to the equilibrium two-state models previously proposed for representatives of classes alpha/pi/Sj26 GSTs. Class mu subunits appear to be intrinsically more stable than those of the other GST classes.