The long-term impacts of COVID-19 on confirmed cases at least 12 months post-infection in Wellington, New Zealand: an observational, cross-sectional study.

AIM: To explore the prevalence of ongoing symptoms and laboratory abnormalities in confirmed cases of COVID-19 from the first wave within the Greater Wellington Region, after at least 12 months post infection. METHOD: COVID-19 cases were obtained from EpiSurv. Eligible participants electronically completed questionnaires (Overall Health Survey, Patient Health Questionnaire-9 [PHQ-9], Generalised Anxiety Disorder-7 [GAD-7], Pittsburgh Sleep Quality Index, EuroQol 5 Dimension 5 Level [EQ-5D-5L], Fatigue Severity Scale [FSS], WHO Symptom Questionnaire, Modified Medical Research Council Dyspnoea Scale [mMRC Dyspnoea Scale]). Blood samples were analysed for cardiac, endocrine, haematological, liver, antibody, and inflammatory markers. RESULTS: Forty-two of 88 eligible cases undertook the study. Participants were enrolled at a median 628.5 days from symptom onset. Fifty-two point four percent felt that their current overall health was worse than it was prior to contracting COVID-19. Ninety percent of participants reported at least two ongoing symptoms since their acute illness. Between 45-72% of participants reported each of anxiety, depression, dyspnoea, pain/discomfort, and sleep difficulties, assessed using the GAD-7, PHQ-9, mMRC Dyspnoea Scale, EQ-5D-5L and FSS questionnaires respectively. There were minimal laboratory abnormalities. CONCLUSION: There is a high prevalence of ongoing symptoms following the first wave of COVID-19 infection in Aotearoa New Zealand. At a median of 1.7 years post infection, there is a wide spectrum of symptoms and symptom severity, although as an observational, cross-sectional study a causal relationship between symptoms or their severity and COVID-19 infection cannot be firmly established.

When should a longer needle be used for intramuscular injection in obese patients? A combined analysis of New Zealand data.

AIM: To estimate thresholds for Body Mass Index (BMI) and arm circumference above which a longer needle is needed to ensure intramuscular (IM) delivery of a vaccine in the deltoid muscle at the site recommended by New Zealand (NZ) immunization guidelines. METHODS: A combined analysis of two studies, including 442 adults, with measurements of arm circumference, BMI and skin to deltoid muscle distance (SDMD) at the NZ immunization guideline-recommended IM injection site. Receiver Operator Characteristic curves identified arm circumference and BMI cut-points that gave 100% sensitivity for SDMD thresholds. These thresholds were: SDMD of 20 mm, accounting for a minimal penetration of 5 mm into muscle with the standard needle; and 25 mm, which is the length of a standard needle for IM injection, representing the depth this can reach. RESULTS: Cut-point values for arm circumference, at which a longer needle would be required, were higher for males than females: 35 cm versus 30 cm for the 20 mm cut-point, and 40 cm versus 36.7 cm for the 25 mm cut-point respectively. The BMI cut-points were also higher for male than females: 24.6 kg/m2 versus 23.7 kg/m2 for the 20 mm cut-point, and 38.2 kg/m2 vs 31.6 kg/m2 for the 25 mm cut-point respectively. CONCLUSION: Arm circumference and BMI cut-points provide practical measures from which to choose a needle length that increases the chance of successful IM vaccination. Based on our data, an arm circumference of 35 cm for men and 30 cm for women should prompt selection of a longer needle to ensure intramuscular injection at the deltoid site. Thresholds for the different skin to deltoid sites proposed internationally should be determined to enable successful IM vaccination in clinical practice beyond NZ.

Single dose of budesonide/formoterol turbuhaler compared to salbutamol pMDI for speed of bronchodilator onset in asthma: a randomised cross-over trial.

OBJECTIVE: To compare bronchodilator response after to salbutamol and budesonide/formoterol in adults with stable asthma. METHODS: A double-blind, cross-over, single-centre, placebo-controlled, non-inferiority trial. Adults with stable asthma were randomised to different orders of two treatment regimens: two actuations of placebo via MDI and one actuation of budesonide/formoterol 200/6 µg via turbuhaler; and one actuation of placebo turbuhaler and two actuations of salbutamol 100 µg via MDI. The primary outcome measure was FEV1 after 2 min. Secondary outcome measures included FEV1, mBorg Dyspnoea Scale score and visual analogue score for breathlessness over 30 min. RESULTS: Forty-nine of 50 potential participants were randomised. One participant withdrew following the first intervention visit and another could not be randomised due to COVID-19 restrictions. The mean (SD) change from baseline FEV1 2 min after treatment administration for budesonide/formoterol and salbutamol was 0.08 (0.14) L, n=49, and 0.17 (0.18) L, n=48, respectively, mean (95% CI) paired difference of -0.097 L (-0.147 to -0.047), p=0.07, against a non-inferiority bound of -0.06 L. In the secondary analysis, FEV1 over 30 min was lower for budesonide/formoterol compared with salbutamol, difference (95% CI): -0.10 (-0.12 to -0.08) L, p<0.001. There were no differences in Visual Analogue Scale score or mBorg Dyspnoea Scale score between treatments. CONCLUSION: The results do not support the primary hypothesis of non-inferiority at the boundary of -0.06 L for the difference between budesonide/formoterol 200/6 µg compared with salbutamol 200 µg for FEV1 at 2 min, and could be consistent with inferiority with a p value of 0.07. For the secondary analysis of FEV1 measurements over time, the FEV1 was higher with salbutamol. TRIAL REGISTRATION NUMBER: Australian and New Zealand Clinical Trials Registry (ACTRN 12619001387112).

Clinical features of patients hospitalised with COVID-19 from February to October 2020, during the early waves of the pandemic in New Zealand.

AIM: As New Zealand transitions towards endemic SARS-CoV-2, understanding patient factors predicting severity, as well as hospital resourcing requirements will be essential for future planning. METHODS: We retrospectively enrolled patients hospitalised with COVID-19 from 26 February to 5 October 2020 as part of the COVID-19 HospitalisEd Patient SeverIty Observational Study NZ (COHESION). Data on demographics, clinical course and outcomes were collected and analysed as a descriptive case series. RESULTS: Eighty-four patients were identified across eight district health boards. Forty-one (49%) were male. The median age was 58 years [IQR: 41.7-70.3 years]. By ethnicity, hospitalisations included 38 NZ European (45%), 19 Pasifika (23%), 13 Maori (15%), 12 Asian (14%) and 2 Other (2%). Pre-existing co-morbidities included hypertension (26/82, 32%), obesity (16/66, 24%) and diabetes (18/81, 22%). The median length of stay was four days [IQR: 2-15 days]. Twelve patients (12/83, 14%) were admitted to an intensive care unit or high dependency unit (ICU/HDU). Ten (10/83, 12%) patients died in hospital of whom seven (70%) were not admitted to ICU/HDU; the median age at death was 83 years. CONCLUSION: Despite initially low case numbers in New Zealand during 2020, hospitalisation with COVID-19 was associated with a high mortality and hospital resource requirements.

How best to share research with study participants? A randomised crossover trial comparing a comic, lay summary, and scientific abstract.

Healthcare research is traditionally published in academic papers, coded in scientific language, and locked behind paywalls - an inaccessible form for many. Sharing research results with participants and the public in an appropriate, accessible manner, is an ethical practice directed in research guidance. Evidence-based recommendations for the medium used are scant, but science communication advice advocates principles which may be fulfilled well by the medium of comics. We report a randomised crossover study conducted online, comparing participant preferences for research results shared in the medium of a comic, a traditional lay text summary, and the control approach of a scientific abstract. 1236 respondents read all three summaries and ranked their most and least preferred formats. For the most preferred summary, the comic was chosen by 716 (57.9%), lay summary by 321 (26.0%), and scientific abstract by 199 (16.1%) respondents. For the least preferred summary the scientific abstract was chosen by 614 (49.7%), lay summary by 380 (30.7%) and comic by 242 (19.6%). Review of free-text responses identified key reasons for the majority preferring the comic over the others, which included finding this easier to read and understand, more enjoyable to consume, and more satisfactory as a medium of communication.

Repeated dose budesonide/formoterol compared to salbutamol in adult asthma: A randomised cross-over trial.

OBJECTIVE: To determine the comparative bronchodilator, systemic beta2-agonist, cardiovascular and adverse effects of salbutamol 200 µg and budesonide/formoterol 200/6 µg when taken repeatedly in stable asthma. METHODS: This open-label, cross-over, single-centre, controlled trial, randomised adults with asthma to different orders of two treatment regimens: salbutamol 200 µg via MDI at t=0, 30, 60, 90 min, then salbutamol 2.5 mg via nebuliser at t=120, 140, 160 and 420 min; or budesonide/formoterol 200/6 µg one actuation via Turbuhaler at t=0, 30, 60, 90 min, two actuations at t=120, 140, 160 and 420 min. The primary outcome measure was FEV1 after 180 min. Secondary outcomes included repeat measures of FEV1, serum potassium, heart rate, and adverse events RESULTS: Of 39 patients randomised, two withdrew due to adverse events (QTCF prolongation and T wave abnormalities) after the first intervention with salbutamol. The mean (sd) change from baseline FEV1 180 min after randomisation for salbutamol and budesonide/formoterol regimens was 0.71 (0.46) L, N=38, and 0.58 (0.45) L, N=37, respectively; with a mean (sd) paired difference of -0.10 (0.40) L, N=37, and a model-based estimated difference (95% CI) -0.12 (-0.25 to 0.02) L, p=0.088. In the main secondary analysis, salbutamol resulted in significantly greater FEV1 from 30 to 240 min, but lesser FEV1 at 360 and 420 min. Salbutamol resulted in a significantly lower serum potassium, and a higher heart rate and number of adverse events. CONCLUSION: The comparative bronchodilator responses of repeated administration of salbutamol 200 µg dose-1 and budesonide/formoterol 200/6 µg differed depending on the time of measurement. Salbutamol caused greater systemic beta2-agonist and cardiovascular effects and more adverse events.

Audit of oxygen administration to achieve a target oxygen saturation range in acutely unwell medical patients.

PURPOSE OF THE STUDY: To evaluate documentation of a target oxygen saturation (SpO2) range and ability to achieve this range in acutely unwell inpatients. STUDY DESIGN: In this single-centre audit, patients with discharge diagnoses of pneumonia, heart failure and exacerbation of asthma or COPD admitted to Wellington Regional Hospital, New Zealand between 1 June 2019 and 31 August 2019 who received oxygen were identified. In those with a documented target SpO2 range, the proportion of SpO2 measurements in the observation chart which were within, above and below range were determined as well as the maximum and minimum SpO2. Regression analysis was performed to determine whether these outcomes were influenced by the prescribed range, high-dependency care or the number of adjustments to oxygen administration. RESULTS: 268 admissions were screened. Of the 100 eligible admissions who received oxygen, a target SpO2 range was documented in 62. The mean (SD) proportion of SpO2 measurements within range was 56.2 (30.6)%. A hypercapnic target SpO2 range was associated with a higher probability of an SpO2 above range; multivariate OR 5.34 (95% CI 1.65 to 17.3, p=0.006) and a lower probability of an SpO2 below range; multivariate OR 0.25 (95% CI 0.08 to 0.80) p=0.02. The mean (SD) maximum SpO2 was similar in those with a target range of 92%-96% versus a hypercapnic range; 96.2 (3.0)% and 95.2 (3.4)%, respectively. CONCLUSIONS: Oxygen prescription and delivery in this clinical setting was suboptimal. SpO2 values above the designated range are common, particularly in patients with a hypercapnic target range.

Rhinothermy delivered by nasal high flow therapy in the treatment of the common cold: a randomised controlled trial.

BACKGROUND: The common cold is the most common infectious disease affecting humans and has a substantial economic impact on society. Human rhinoviruses, which cause almost two-thirds of colds, have demonstrated temperature-dependent replication which is optimal between 33°C and 35°C. METHODS: This randomised, single-blind, parallel-group trial completed at a single-centre in New Zealand, recruited 170 participants aged 18-75 years (mean age 27.5 years) who were within 48 hours of common cold symptom onset and had a symptom score (the Modified Jackson Score (MJS)) ≥7 and a negative point-of-care test for influenza. Participants were blinded to the intervention and randomised (1:1) to 5 days of either nasal high flow rhinothermy (rNHF) (100% humidified air delivered at 35 L/min and 41°C for 2 hours daily) (n=85) or 'sham' rhinothermy (100% humidified air delivered at 10 L/min and 31°C for 10 min daily) (n=85) and completed daily symptom diaries, which included the MJS, for 14 days, to investigate whether rNHF reduced common cold symptom severity and duration compared with 'sham' rhinothermy. RESULTS: An intention-to-treat superiority analysis included all randomised participants and showed no difference between treatment groups for the primary outcome, the day 4 MJS analysed by analysis of covariance: mean (SD) 6.33 (3.97) for rNHF vs 5.8 (3.15) for 'sham'; estimated difference (95% CI) 0.37 (-0.69 to 1.42), p=0.49. There was no difference in time until resolution of symptoms: mean (SD) 5.96 (4.47) days for rNHF vs 6.42 (4.09) days for 'sham'; estimated difference (95% CI) 1.02 (0.75 to 1.38), p=0.91. There were no serious adverse events related to the study treatments. CONCLUSIONS: This well-powered, single-blind randomised controlled trial does not provide evidence that 5 days of rNHF (100% humidified air heated to 41°C delivered at 35 L/min for 2 hours daily) reduces common cold symptom severity or duration. However, investigation of rNHF in the treatment of influenza is warranted. TRIAL REGISTRATION NUMBER: ACTRN12617001340325.

Determination of oxygen saturation compared to a prescribed target range using continuous pulse oximetry in acutely unwell medical patients.

BACKGROUND: Both inadequate and excessive administration of oxygen to acutely unwell patients results in risk of harm. Guidelines recommend titration of oxygen to achieve a target oxygen saturation (SpO2) range. Information regarding whether this is being achieved is limited. METHODS: In this two-centre non-interventional study we used continuous pulse oximetry in acutely unwell medical patients over a 24-h period to determine the proportion of time spent with SpO2 within the prescribed target range and whether this is influenced by the target range, age, care in a high-dependency area and the number of oxygen adjustments. RESULTS: Eighty participants were included in the analysis. The mean (SD) proportion of time spent in target range was 55.6% (23.6), this was lower in those with a reduced hypercapnic target range (88-92% or below) compared to those with a range of 92-96%; difference - 13.1% (95% CI - 3.0 to - 23.2), P = 0.012. The proportion of time spent above range was 16.2% (22.9); this was higher in those with a reduced hypercapnic range; difference 21.6% (31.4 to 12), P < 0.001. The proportion of time below range was 28.4% (25.2); there was no difference between target ranges. The proportion of time spent in range was higher for those in a high dependency area in the multivariate model; difference 15.5% (95% CI 2.3 to 28.7), P = 0.02. CONCLUSIONS: Medical patients receiving oxygen in a ward setting spend significant periods of time with SpO2 both above and below the prescribed target range while receiving oxygen therapy.

Clinical and epidemiological characteristics of COVID-19 in Wellington, New Zealand: a retrospective, observational study.

AIMS: To review the demographic and clinical characteristics of confirmed COVID-19 cases within the Greater Wellington Region (GWR). METHODS: A retrospective, observational study of all 96 confirmed COVID-19 cases in the GWR. The primary outcome was time taken from onset to complete resolution of symptoms. Secondary outcomes were the epidemiological and clinical characteristics of cases. RESULTS: The mean (SD) time from symptom onset to complete resolution was 19.1 (1.1) days. The mean (SD) age was 43.1 (16.9). 51% were male. The majority were of European ethnicity (84%), resided in the top five decile neighbourhoods (76%) and had travelled to New Zealand (69%). The mean (SD) time from onset of symptoms to obtaining RT-PCR testing results was 5.3 (0.4) days. The most common symptoms at onset were cough (36%), sore throat (22%) and fatigue (21%); the overall most common symptoms were cough (65%), sore throat (43%), headache (43%) and fatigue (42%); many symptoms were late manifestations. The most common co-morbidity reported was asthma (20%), with no reported exacerbations. The rate of secondary infections within households was 0.05 per primary infection. CONCLUSION: The demography of COVID-19 cases reflected the imported nature of cases. The clinical presentation of COVID-19 was highly variable and there were no particular symptoms that could accurately predict infection.

Automatic versus manual oxygen titration using a novel nasal high-flow device in medical inpatients with an acute illness: a randomised controlled trial.

BACKGROUND: Guideline recommendations state oxygen should be administered to acutely unwell patients to achieve a target oxygen saturation (SpO2) range. The current practice of manual oxygen titration frequently results in SpO2 outside of a prescribed range. The aim of this study was to assess the efficacy of automatic oxygen titration using a closed-loop feedback system to achieve SpO2 within a prescribed target range METHODS: An open-label randomised parallel group trial was undertaken comparing automatic oxygen titration using a novel nasal high-flow device to manual oxygen titration using nasal high flow. Medical inpatients requiring oxygen therapy in Wellington Regional Hospital, New Zealand with a prescribed target SpO2 range of 88%-92% or 92%-96% were recruited and randomised equally between the interventions for a period of 24 hours. The primary outcome was the proportion of time spent with SpO2 within the prescribed range. RESULTS: 20 patients were included in the analysis. Automatic oxygen titration resulted in a median (IQR) 96.2% (95.2-97.8) of time within the target range compared with 71% (59.4-88.3) with manual titration; difference (95% CI) 24.2% (7.9% to 35%), p<0.001. There was a reduction in the time spent with SpO2 ≥2% above and ≥2% below range in the automatic titration group, although the point estimate for the differences were small; -1% (-8.2% to -0.04%), p=0.017 and -2.4% (-11.5% to 0.3%), p=0.05 respectively. CONCLUSIONS: Nasal high-flow with automatic oxygen titration resulted in a greater proportion of time spent with SpO2 in target range compared with manual titration. TRIAL REGISTRATION: The trial was registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12619000901101).

Underestimation of COVID-19 mortality during the pandemic.

BACKGROUND: There has been considerable international variation in mortality during the COVID-19 pandemic. The objective of this study was to investigate the differences between mortality registered as due to COVID-19 and the excess all-cause mortality reported in countries worldwide during the COVID-19 pandemic. METHODS: Ecological analysis of 22 countries compared 5-year historical all-cause mortality, reported all-cause mortality and expected all-cause mortality (calculated as historical mortality plus the reported deaths attributed to COVID-19). Data available from the first week of January 2020 to that most recently available were analysed. RESULTS: Compared to the preceding 5 years, there was an excess of 716 616 deaths, of which 64.3% were attributed to COVID-19. The proportion of deaths registered as COVID-19-related/excess deaths varied markedly between countries, ranging between 30% and 197% in those countries that had an excess of deaths during the period of observation. In most countries where a definite peak in COVID-19-related deaths occurred, the increase in reported all-cause mortality preceded the increase in COVID-19 reported mortality. During the latter period of observation, a few countries reported fewer all-cause deaths than the historical figures. CONCLUSION: The increases in all-cause mortality preceded the increase in COVID-19 mortality in most countries that had definite spikes in COVID-19 mortality. The number of deaths attributed to COVID-19 was underestimated by at least 35%. Together these findings suggest that calculation of excess all-cause mortality is a better predictor of COVID-19 mortality than the reported rates, in those countries experiencing definite increases in mortality.

How big is your bubble? Characteristics of self-isolating household units ('bubbles') during the COVID-19 Alert Level 4 period in New Zealand: a cross-sectional survey.

OBJECTIVE: To characterise the self-isolating household units (bubbles) during the COVID-19 Alert Level 4 lockdown in New Zealand. DESIGN, SETTING AND PARTICIPANTS: In this cross-sectional study, an online survey was distributed to a convenience sample via Facebook advertising and the Medical Research Institute of New Zealand's social media platforms and mailing list. Respondents were able to share a link to the survey via their own social media platforms and by email. Results were collected over 6 days during Alert Level 4 from respondents living in New Zealand, aged 16 years and over. MAIN OUTCOMES MEASURES: The primary outcome was the mean size of a self-isolating household unit or bubble. Secondary outcomes included the mean number of households in each bubble, the proportion of bubbles containing essential workers and/or vulnerable people, and the mean number of times the home was left each week. RESULTS: 14 876 surveys were included in the analysis. The mean (SD) bubble size was 3.58 (4.63) people, with mean (SD) number of households 1.26 (0.77). The proportion of bubbles containing one or more essential workers, or one or more vulnerable persons was 45.3% and 42.1%, respectively. The mean number of times individual bubble members left their home in the previous week was 12.9 (12.4). Bubbles that contained at least one vulnerable individual had fewer outings over the previous week compared with bubbles that did not contain a vulnerable person. The bubble sizes were similar by respondent ethnicity. CONCLUSION: In this New Zealand convenience sample, bubble sizes were small, mostly limited to one household, and a high proportion contained essential workers and/or vulnerable people. Understanding these characteristics from a country which achieved a low COVID-19 infection rate may help inform public health interventions during this and future pandemics.

Using comics and curiosity to drive pandemic research on a national scale.

An independent online Public Health survey regarding the COVID-19 pandemic was conducted during an Alert Level 4 lockdown, the highest possible, in New Zealand. An illustrated and curiosity-driven public engagement campaign was designed to advertise survey participation, and performance compared with a standard approach using randomised controlled A/B Split tests. The 'Caretoon' approach featured comic illustrations, appealed to goodwill and was intended to pique curiosity. This linked to an illustrated version of the survey which, upon completion, gave a personalised comic summary showing how respondent's answers compared with national averages. The standard ad and survey were not illustrated with comics, and did not provide a personalised comic summary on completion. Both approaches were cost- and time-effective, together resulting in 18,788 responses over six days. The Caretoon approach outperformed the standard approach in terms of the number of people reached, engaged, survey link clicks, gender and ethnic diversity amongst respondents, and cost-effectiveness of advertising. This came at the expense of a small reduction in the proportion of completed surveys and male respondents. The research evidences objective value of public engagement activity, comics and curiosity as tools which can support Public Health research on a national scale.

Closed-Loop Oxygen Control Using a Novel Nasal High-Flow Device: A Randomized Crossover Trial.

BACKGROUND: Oxygen administration is recommended for patients with hypoxemia to achieve a target [Formula: see text] range. Strategies to achieve this in clinical practice are suboptimal. We investigated automatic oxygen titration using a novel nasal high-flow device with closed-loop oxygen control. The objective of this proof-of-concept study was to determine whether closed-loop control was able to respond to desaturation and subsequent recovery in a controlled laboratory-based environment. METHODS: We conducted a single-blind randomized crossover trial in adults with chronic respiratory disease who had a resting [Formula: see text] ≥ 92% and desaturated to < 90% during a 6-min walk test (6MWT). Nasal high-flow was administered during a 6MWT and a subsequent 10-min rest period with either room air, a fixed concentration of 28% oxygen, or oxygen titrated automatically using closed-loop control. RESULTS: The study involved 42 subjects. Closed-loop control maintained [Formula: see text] within the target range of 92-96% for a mean (SD) duration of 54.4 ± 30.1% of the 6MWT and 67.3 ± 26.8% of the recovery period. The proportion of time spent with an [Formula: see text] in the target range during the 6MWT was significantly greater for closed-loop control compared to room air, with a difference of 26.0% (95% CI 17.7-34.2, P < .001); this proportion of time was not significantly different compared to the fixed concentration of 28% oxygen, with a difference of -8.2% (95% CI -16.5 to 0.1, P = .052). The proportion of time spent in the target range during the rest period was significantly greater compared to 28% oxygen, with a difference of 19.3% (95% CI 8.9-29.7, P < .001); this proportion of time was not significantly different compared to room air, with a difference of -9.3% (95% CI -19.7 to 1.0, P = .08). CONCLUSIONS: This study provides proof-of-concept evidence that the novel nasal high-flow device with closed-loop control can respond to changes in [Formula: see text] outside a target saturation range using a model of exercise-induced desaturation and subsequent recovery.