Clinical trial: An open-label, randomised trial of different re-start strategies after treatment withdrawal in HBeAg negative chronic hepatitis B.

BACKGROUND: Stopping nucleos(t)ide analogue (NA) therapy in patients with chronic hepatitis B (CHB) may trigger a beneficial immune response leading to HBsAg loss, but clinical trials on re-start strategies are lacking. AIM: To assess whether it is beneficial to undergo a prolonged flare after NA cessation. METHODS: One-hundred-and-twenty-seven patients with HBeAg negative, non-cirrhotic CHB with at least 24 months of viral suppression on NA therapy were included. All study participants stopped antiviral therapy and were randomised to either low-threshold (ALT > 80 U/L and HBV DNA > 2000 IU/mL) or high-threshold (ALT > 100 U/L for >4 months, or ALT > 400 U/L for >2 months) for the re-start of therapy. The primary endpoint was HBsAg loss within 36 months of stopping antiviral treatment. The primary analysis was based on intention-to-treat allocation with last observation carried forward. RESULTS: There was a numerical but not statistically significant difference in HBsAg loss between the low-threshold (3 of 64; 4.7%) and the high-threshold (8 of 63; 12.7%) group (risk difference: 8.0%, 95% CI: -2.3 to 19.6, p = 0.123). None of the patients with end-of-treatment HBsAg > 1000 IU/mL achieved HBsAg loss; among those with end-of-treatment HBsAg < 1000 IU/mL, 8 of 15 (53.3%) achieved HBsAg loss in the high-threshold group compared to 3 of 26 (11.5%) in the low-threshold group. CONCLUSIONS: We could not confirm our hypothesis that a higher threshold for restart of therapy after NA withdrawal improves the likelihood of HBsAg loss within 36 months in patients with HBeAg negative CHB. Further studies including only patients with HBsAg level <1000 IU/mL and/or larger sample size and longer follow-up duration are recommended.

Sykdomsforløp blant pasienter innlagt på Bærum sykehus med delta- og omikronvariantene av SARS-CoV-2-viruset.

BACKGROUND: Waves of infection have formed the pattern of the COVID-19 pandemic. A wave dominated by the delta variant of the SARS-CoV-2 virus in autumn 2021 was superseded by the omicron variant over the course of a few weeks around Christmas. We describe how this transition affected the population of patients admitted to a Norwegian local hospital with COVID-19. MATERIAL AND METHOD: All patients admitted to Bærum Hospital with confirmed SARS-CoV-2 virus were included in a quality study which aimed to describe patient characteristics and clinical course. We present patients admitted in the periods 28 June 2021-31 December 2021 and 1 January 2022-12 June 2022, described here as the delta wave and the omicron wave. RESULTS: The SARS-CoV-2-virus was confirmed in a total of 144 patients who were admitted during the delta wave, and in 261 patients during the omicron wave, where 14/144 (10 %) and 89/261 (34 %) were admitted for reasons other than COVID-19. Patients with COVID-19 during the delta wave were younger on average (59 vs. 69 years) and had a lower Charlson comorbidity index score (2.6 vs. 4.9) and a lower Clinical Frailty Scale score (2.8 vs. 3.7) than patients in the omicron wave. Among 302/405 patients admitted with COVID-19 as the principal diagnosis, 88/130 (68 %) patients had respiratory failure during the delta wave and 59/172 (34 %) during the omicron wave, with a median number of 8 bed days (interquartile range 5-15) and 5 (interquartile range 3-8). INTERPRETATION: The transition from the wave of infection that was dominated by the delta variant of the SARS-CoV-2 virus to the wave dominated by the omicron variant had a considerable effect on the characteristics and clinical course of patients admitted to hospital with SARS-CoV-2 infection.

Three waves of COVID-19 in a Norwegian local hospital. / Tre bølger med covid-19 på et norsk lokalsykehus.

BACKGROUND: The objective of this article is to summarise the course of illness and treatment for patients with COVID-19 admitted to Bærum Hospital since the start of the pandemic. MATERIAL AND METHOD: We present data from a prospective observational study with the aim of systematising knowledge about patients admitted because of COVID-19. All patients admitted to Bærum Hospital up to and including 28 June 2021 were included. The results are presented for three waves of admissions: 9 March-23 June 2020, 21 September 2020-28 February 2021 and 1 March-28 June 2021. RESULTS: A total of 300 patients, divided into 77, 101 and 122 in the three waves respectively, were admitted because of COVID-19. The number of hospital deaths during the three waves was 14 (18 %), 11 (11 %) and 5 (4 %) respectively. The average age of the patients was 67.6 years in the first wave and 53.3 years in the third wave. Altogether 204 patients (68 %) received medical oxygen or ventilation support, and 31 of these (10 % of all the patients) received invasive ventilation support. Non-invasive ventilation support was used as the highest level of treatment in 4 (8 %), 9 (13 %) and 17 (20 %) patients with respiratory failure in the three waves respectively. In the second and third wave, 125 out of 152 patients with respiratory failure (82 %) were treated with dexamethasone. INTERPRETATION: Differences in patient characteristics and changes to treatment methods, such as the use of dexamethasone and non-invasive ventilation support, may have contributed to the apparent fall in mortality from the first to the third wave. Conditions that are not registered in the study, such as vaccination status, may also have impacted on mortality.

An immunosuppressed woman in her seventies with night sweats and weight loss. / En immunsupprimert kvinne i 70-årene med nattesvette og vekttap.

BACKGROUND: Candidatus Neoehrlichia mikurensis is an emerging tick-borne pathogen with widespread distribution in Ixodes ricinus ticks in Europe and Asia. It has been found to cause chronic infections, particularly in immunosuppressed individuals. Common symptoms include relapsing fever, night sweats and thromboembolic episodes, likely due to endovascular infection. CASE PRESENTATION: A patient in her seventies developed persistent night sweats and moderate weight loss that persisted for four months prior to evaluation. There was no history of fever or organ-specific symptoms. Prior diseases included a ten-year history of rheumatoid arthritis treated with rituximab. Initial workup revealed moderately increased acute phase reactants, but no evidence of malignant disease or endocrine abnormalities. Night sweats persisted, and after eight months moderate splenic enlargement was observed. PCR revealed presence of Candidatus Neoehrlichia mikurensis DNA, and symptoms resolved promptly after initiation of oral doxycycline treatment. INTERPRETATION: Infection with anaplasmataceae such as Candidatus Neoehrlichia mikurensis can present with non-specific constitutive symptoms. In this case, persistent night sweats and moderate weight loss were the only manifestations over an eight-month period. Diagnosis is readily established by PCR analysis of whole blood, but a high degree of suspicion and careful assessment of potential exposure is required for timely diagnosis.

Complications and mortality among patients hospitalised with COVID-19. / Komplikasjoner og dødelighet blant pasienter innlagt med covid-19.

BACKGROUND: The course of disease, complications and hospital mortality among patients with COVID-19 admitted to Norwegian hospitals has not been widely described. The purpose of this study was to survey patients with COVID-19 admitted to a local hospital. MATERIAL AND METHOD: The data were retrieved from a prospective observational study of all patients admitted with COVID-19 to Bærum Hospital since the start of the coronavirus outbreak. RESULTS: A total of 73 patients with COVID-19 admitted in the period 9 March 2020-7 May 2020 were included. The mean age was 67.9 years, and 43 patients (59 %) were men. The average number of days hospitalised was 10.1. Altogether 19 patients (26 %) had a very severe course of disease, and 14 (19 %) died during their stay in hospital. The mean age among the patients who died was 79.5 years. A total of 49 patients (67 %) had hypoxaemia and required oxygen therapy for an average of 10.1 days. Of these, 9 patients were given invasive respiratory support for a median 18 days. Symptoms of delirium occurred in 26 patients (36 %) and was the most frequent non-respiratory complication. INTERPRETATION: The majority of the patients hospitalised with COVID-19 needed prolonged oxygen therapy, and there was a high incidence of severe complications.

Pulmonary embolism in cases of COVID-19. / Lungeembolisme ved covid-19.

BACKGROUND: Emerging reports indicate a high incidence of venous thromboembolism in patients hospitalised for SARS-CoV-2 pneumonia during the spring 2020 pandemic. The pronounced pulmonary and systemic inflammatory responses observed in these patients may contribute to a transient hypercoagulable state. In this setting, pulmonary embolism may cause further respiratory distress and clinical deterioration. CASE PRESENTATION: We describe the clinical course of three patients admitted with SARS-CoV-2 infection and respiratory distress, where pulmonary embolism was detected during the course of the hospitalisation. Two of the cases occurred despite early institution of standard dosage of low molecular weight heparin thromboprophylaxis, and in one case, pulmonary embolism was diagnosed during the convalescent phase of an otherwise benign COVID-19 disease course. INTERPRETATION: These cases highlight the importance of awareness of the potentially increased incidence of venous thromboembolism in COVID-19 disease. Further research is required to establish appropriate clinical management guidelines for prevention of thromboembolic complications in COVID-19.

Mechanical chest compressions with trapezoidal waveform improve haemodynamics during cardiac arrest.

BACKGROUND: During manual chest compressions for cardiac arrest the waveforms of chest compressions are generally sinusoidal, whereas mechanical chest compression devices can have different waveforms, including trapezoidal. We studied the haemodynamic differences of such waveforms in a porcine model of cardiac arrest. METHODS: Eight domestic pigs (weight 31±3kg) were anaesthetised and instrumented to continuously monitor aortic (AP) and right atrial pressure (RAP), carotid (CF) and cerebral cortical microcirculation blood flow (CCF). Coronary perfusion pressure (CPP) was calculated as the maximal difference between AP and RAP during diastole or decompression phase. After 4 min of electrically induced ventricular fibrillation, mechanical chest compressions were performed with four different waveforms in a factorial design, and in randomized sequence for 3 min each. Resulting differences are presented as mean with 95% confidence intervals. RESULTS: Mean AP and RAP were higher with trapezoid than sinusoid chest compressions, difference 5.7 (0.7, 11) and 6.3 (2.1, 11)mmHg, respectively. Flow measured as CF and CCF was also improved with trapezoidal waveform, difference 14 (2.8, 26)ml/min and 11 (5.6, 17)% of baseline, respectively, with a parallel, non-significant (P=0.08) trend for CPP. Active vs. passive decompression to zero level improved CF, but without even a trend for CPP. CONCLUSION: Trapezoid chest compressions and active decompression to zero level improved blood flow to the brain. The compression waveform is an additional factor to consider when comparing mechanical and manual chest compressions and when comparing different compression devices.

[Severe ethylene glycol poisoning treated wtih fomepizole (4-methylpyrazole)]. / Alvorlig etylenglykolforgiftning behandlet med fomepizol (4-metylpyrazol).

BACKGROUND: Poisoning with ethylene glycol causes severe metabolic acidosis and renal failure, and is potentially lethal if not treated rapidly. Until recently the standard therapy for this poisoning has been bicarbonate to counteract the metabolic acidosis, inhibition of alcohol dehydrogenase (ADH) with ethanol to prevent the production of toxic metabolites and haemodialysis to remove ethylene glycol and its toxic metabolites. The new potent inhibitor of ADH, 4-methylpyrazole (fomepizole), has recently been approved for the treatment of methanol and ethylene glycol poisonings. MATERIAL AND METHODS: Three patients severely poisoned by ethylene glycol and treated with fomepizole are presented. RESULTS: Of our three patients treated with fomepizole two were managed without haemodialysis. One patient had an exceptionally high serum ethylene glycol concentration (90 mmol/l; 585 mg/dl) and was successfully treated with fomepizole without the need for haemodialysis despite pronounced metabolic acidosis. INTERPRETATION: Ethylene glycol poisonings may be treated effectively with fomepizole without haemodialysis.