Background Neurologic manifestations are well-recognized features of coronavirus disease 2019 (COVID-19). However, the longitudinal association of biomarkers reflecting CNS impact and neurological symptoms is not known. We sought to determine whether plasma biomarkers of CNS injury were associated with neurologic sequelae after COVID-19. Methods Patients with confirmed acute COVID-19 were studied prospectively. Neurological symptoms were recorded during the acute phase of the disease and at six months follow-up, and blood samples were collected longitudinally. Healthy age-matched individuals were included as controls. We analysed plasma concentrations of neurofilament light-chain (NfL), glial fibrillary acidic protein (GFAp), and growth differentiation factor 15 (GDF-15). Findings One hundred patients with mild ( n = 24), moderate ( n = 28), and severe ( n = 48) COVID-19 were followed for a median (IQR) of 225 (187–262) days. In the acute phase, patients with severe COVID-19 had higher concentrations of NfL than all other groups (all p < 0·001), and higher GFAp than controls ( p < 0·001). GFAp was also significantly increased in moderate disease ( p < 0·05) compared with controls. NfL ( r = 0·53, p < 0·001) and GFAp ( r = 0·39, p < 0·001) correlated with GDF-15 during the acute phase. After six months, NfL and GFAp concentrations had normalized, with no persisting group differences. Despite this, 50 patients reported persistent neurological symptoms, most commonly fatigue ( n = 40), “brain-fog” ( n = 29), and changes in cognition ( n = 25). We found no correlation between persistent neurological symptoms and CNS injury biomarkers in the acute phase. Interpretation The normalization of CNS injury biomarkers in all individuals, regardless of previous disease severity or persisting neurological symptoms, indicates that post COVID-19 neurological sequelae are not accompanied by ongoing CNS injury. Funding The Swedish State Support for Clinical Research, SciLifeLab Sweden, and the Knut and Alice Wallenberg Foundation have provided funding for this project.

Background: Primary care has a crucial role in responding to the COVID-19 pandemic as the first point of patient care and gatekeeper to secondary care. Qualitative studies exploring the experiences of healthcare professionals during the COVID-19 pandemic have mainly focused on secondary care. Aim: To understand the experiences of European PCPs working during the first peak of the COVID-19 pandemic. Design and Setting: An exploratory qualitative study, using semi-structured interviews in primary care in England, Belgium, the Netherlands, Ireland, Germany, Poland, Greece and Sweden, between April and July 2020. Method: Interviews were audio recorded, transcribed and analysed using a combination of inductive and deductive thematic analysis techniques. Results: Eighty interviews were conducted with PCPs. PCPs had to make their own decisions on how to rapidly transform services in relation to COVID-19 and non-COVID-19 care. Despite being overwhelmed with guidance, they often lacked access to practical training. Consequently, PCPs turned to their colleagues for moral support and information to try to quickly adjust to new ways of working, including remote care, and deal with uncertainty. Conclusion: PCPs rapidly transformed primary care delivery despite a number of challenges. Representation of primary care at policy level and engagement with local primary care champions will facilitate easy and coordinated access to practical information on how to adapt services, ongoing training and access to appropriate mental health support services for PCPs. Preservation of autonomy and responsiveness of primary care are critical to preserve the ability for rapid transformation in any future crisis of care delivery.

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A decision tool for suspected UTI in frail older adults was developed based on consensus among an international expert panel. Studies are needed to evaluate whether this decision tool is effective in reaching its aim: the improvement of diagnostic evaluation and treatment for suspected UTI in frail older adults.

BackgroundThe high prevalence of bacteriuria in elderly individuals makes it difficult to know if a new symptom is related to bacteria in the urine. There are different views concerning this relationship and bacteriuria often leads to antibiotic treatments. The aim of this study was to investigate the relationship between bacteria in the urine and new or increased restlessness, fatigue, confusion, aggressiveness, not being herself/himself, dysuria, urgency and fever in individuals at nursing homes for elderly when statistically considering the high prevalence of asymptomatic bacteriuria in this population.MethodsIn this cross-sectional study symptoms were registered and voided urine specimens were collected for urinary cultures from 651 elderly individuals. Logistic regressions were performed to evaluate the statistical correlation between bacteriuria and presence of a symptom at group level. To estimate the clinical relevance of statistical correlations at group level positive and negative etiological predictive values (EPV) were calculated.ResultsLogistic regression indicated some correlations at group level. Aside from Escherichia coli in the urine and not being herself/himself existing at least one month, but less than three months, EPV indicated no clinically useful correlation between any symptoms in this study and findings of bacteriuria.ConclusionsUrinary cultures provide little or no useful information when evaluating diffuse symptoms among elderly residents of nursing homes. Either common urinary tract pathogens are irrelevant, or urine culture is an inappropriate test.

BackgroundUp to half the residents of nursing homes for the elderly have asymptomatic bacteriuria (ABU), which should not be treated with antibiotics. A complementary test to discriminate between symptomatic urinary tract infections (UTI) and ABU is needed, as diagnostic uncertainty is likely to generate significant antibiotic overtreatment. Previous studies indicate that Interleukin-6 (IL-6) in the urine might be suitable as such a test. The aim of this study was to investigate the association between laboratory findings of bacteriuria, IL-6 in the urine, dipstick urinalysis and newly onset symptoms among residents of nursing homes.MethodsIn this cross sectional study, voided urine specimens for culture, urine dipstick and IL-6 analyses were collected from all residents capable of providing a voided urine sample, regardless of the presence of symptoms. Urine specimens and symptom forms were provided from 421 residents of 22 nursing homes. The following new or increased nonspecific symptoms occurring during the previous month were registered; fatigue, restlessness, confusion, aggressiveness, loss of appetite, frequent falls and not being herself/himself, as well as symptoms from the urinary tract; dysuria, urinary urgency and frequency.ResultsRecent onset of nonspecific symptoms was common among elderly residents of nursing homes (85/421). Urine cultures were positive in 32% (135/421), Escherichia coli was by far the most common bacterial finding. Residents without nonspecific symptoms had positive urine cultures as often as those with nonspecific symptoms with a duration of up to one month. Residents with positive urine cultures had higher concentrations of IL-6 in the urine (p < 0.001). However, among residents with positive urine cultures there were no differences in IL-6 concentrations or dipstick findings between those with or without nonspecific symptoms.ConclusionsNonspecific symptoms among elderly residents of nursing homes are unlikely to be caused by bacteria in the urine. This study could not establish any clinical value of using dipstick urinalysis or IL-6 in the urine to verify if bacteriuria was linked to nonspecific symptoms.

BackgroundNon-specific symptoms, such as confusion, are often suspected to be caused by urinary tract infection (UTI) and continues to be the most common reason for suspecting a UTI despite many other potential causes. This leads to significant overdiagnosis of UTI, inappropriate antibiotic use and potential harmful outcomes. This problem is particularly prevalent in nursing home settings.MethodsA systematic review of the literature was conducted assessing the association between confusion and UTI in the elderly. PubMed, Scopus and PsychInfo were searched with the following terms: confusion, delirium, altered mental status, acute confusional state, urinary tract infection, urine infection, urinary infection and bacteriuria. Inclusion criteria and methods were specified in advance and documented in the protocol, which was published with PROSPERO (registration ID: CRD42015025804). Quality assessment was conducted independently by two authors. Data were extracted using a standardised extraction tool and a qualitative synthesis of evidence was made.ResultsOne thousand seven hunderd two original records were identified, of which 22 were included in the final analysis. The quality of these included studies varied, with frequent poor case definitions for UTI or confusion contributing to large variation in results and limiting their validity. Eight studies defined confusion using valid criteria; however, no studies defined UTI in accordance with established criteria. As no study used an acceptable definition of confusion and UTI, an association could not be reliably established. Only one study had acceptable definitions of confusion and bacteriuria, reporting an association with the relative risk being 1.4 (95% CI 1.0–1.7, p = 0.034).ConclusionsCurrent evidence appears insufficient to accurately determine if UTI and confusion are associated, with estimates varying widely. This was often attributable to poor case definitions for UTI or confusion, or inadequate control of confounding factors. Future well-designed studies, using validated criteria for UTI and confusion are required to examine the relationship between UTI and acute confusion in the elderly. The optimal solution to clarify this clinical issue would be a randomized controlled trial comparing the effect of antibiotics versus placebo in patients with new onset or worsening confusion and presence of bacteriuria while lacking specific urinary tract symptoms.

Objective To determine whether total exposure to penicillin V can be reduced while maintaining adequate clinical efficacy when treating pharyngotonsillitis caused by group A streptococci. Design Open label, randomised controlled non-inferiority study. Setting 17 primary healthcare centres in Sweden between September 2015 and February 2018. Participants Patients aged 6 years and over with pharyngotonsillitis caused by group A streptococci and three or four Centor criteria (fever ≥38.5°C, tender lymph nodes, coatings of the tonsils, and absence of cough). Interventions Penicillin V 800 mg four times daily for five days (total 16 g) compared with the current recommended dose of 1000 mg three times daily for 10 days (total 30 g). Main outcome measures Primary outcome was clinical cure five to seven days after the end of antibiotic treatment. The non-inferiority margin was prespecified to 10 percentage points. Secondary outcomes were bacteriological eradication, time to relief of symptoms, frequency of relapses, complications and new tonsillitis, and patterns of adverse events. Results Patients (n=433) were randomly allocated to the five day (n=215) or 10 day (n=218) regimen. Clinical cure in the per protocol population was 89.6% (n=181/202) in the five day group and 93.3% (n=182/195) in the 10 day group (95% confidence interval −9.7 to 2.2). Bacteriological eradication was 80.4% (n=156/194) in the five day group and 90.7% (n=165/182) in the 10 day group. Eight and seven patients had relapses, no patients and four patients had complications, and six and 13 patients had new tonsillitis in the five day and 10 day groups, respectively. Time to relief of symptoms was shorter in the five day group. Adverse events were mainly diarrhoea, nausea, and vulvovaginal disorders; the 10 day group had higher incidence and longer duration of adverse events. Conclusions Penicillin V four times daily for five days was non-inferior in clinical outcome to penicillin V three times daily for 10 days in patients with pharyngotonsillitis caused by group A streptococci. The number of relapses and complications did not differ between the two intervention groups. Five day treatment with penicillin V four times daily might be an alternative to the currently recommended 10 day regimen. Trial registration EudraCT 2015-001752-30; ClinicalTrials.gov NCT02712307 .