Signs and symptoms of serious illness in adults with acute abdominal pain presenting to ambulatory care: a systematic review.

BACKGROUND: Acute abdominal pain is a common complaint, caused by a variety of conditions, ranging from acutely life-threatening to benign and self-limiting with symptom overlap complicating diagnosis. Signs and symptoms may be valuable when assessing a patient to guide clinical work. AIM: Summarising evidence on the accuracy of signs and symptoms for diagnosing serious illness in adults with acute abdominal pain in an ambulatory care setting. DESIGN & SETTING: We performed a systematic review, searching for prospective diagnostic accuracy studies who included adults presenting with acute abdominal pain to an ambulatory care setting. METHOD: Six databases and guideline registers were searched, using a comprehensive search strategy. We assessed the risk of bias, calculated descriptive statistics and measures of diagnostic accuracy. Results were pooled when at least four studies were available. RESULTS: Out of 18,923 unique studies, 16 studies with moderate to high-risk bias were included. Fourteen clinical features met our criteria, including systolic blood pressure <100 mmHg (LR +7.01), shock index >0.85, uterine cervical motion tenderness (LR +5.62 and LR- 8.60) and a self-assessment questionnaire score >70 (LR +12.20) or <25 (LR- 0.19). Clinical diagnosis made by the clinician had the best rule-in ability (LR +24.6). CONCLUSIONS: We identified 14 signs and symptoms that can influence the likelihood of a serious illness, including pain characteristics, systemic signs, gynaecological signs and clinician's overall assessment. The risk of bias was moderate to high, leading to uncertainty, preventing us from making firm conclusions. This highlights the need for better research in this setting.

Towards an international consensus on safety netting advice for acutely ill children presenting to ambulatory care: a modified e-Delphi procedure.

OBJECTIVE: Develop a consensus on the content and form of safety netting advice (SNA) for parents of acutely ill children. DESIGN: Four-round modified e-Delphi using online questionnaires and feedback among clinical and research experts. SETTING: Ambulatory care in high-income countries. PARTICIPANTS: Forty-one experts from 13 countries: 3 emergency physicians, 15 general practitioners, 4 nurses and 19 paediatricians. RESULTS: The experts defined the content of SNA as advice on the normal, expected disease course of the provisional diagnosis, diagnostic uncertainty, alarm signs that indicate the need for medical help and information on where and how to find such help. Regarding the form of the SNA, the experts agree that a reliable source should give SNA verbally with paper or digital written or video/image resources at every appropriate healthcare encounter in a short and simple empowering fashion, specific to the child's situation and seek confirmatory feedback from parents. CONCLUSIONS: SNA needs to contain advice on the expected disease course, alarm signs and where and how to find help. It should be given verbally with written resources by a reliable healthcare professional or digital platform. Short, simple and specific, SNA needs to empower the parent whose understanding of the advice should be checked. The effectiveness of SNA resources coproduced by parents and experts should be assessed in different settings and those providing SNA require up-to-date and reliable training.

Antibody tests for identification of current and past infection with SARS-CoV-2.

BACKGROUND: The diagnostic challenges associated with the COVID-19 pandemic resulted in rapid development of diagnostic test methods for detecting SARS-CoV-2 infection. Serology tests to detect the presence of antibodies to SARS-CoV-2 enable detection of past infection and may detect cases of SARS-CoV-2 infection that were missed by earlier diagnostic tests. Understanding the diagnostic accuracy of serology tests for SARS-CoV-2 infection may enable development of effective diagnostic and management pathways, inform public health management decisions and understanding of SARS-CoV-2 epidemiology. OBJECTIVES: To assess the accuracy of antibody tests, firstly, to determine if a person presenting in the community, or in primary or secondary care has current SARS-CoV-2 infection according to time after onset of infection and, secondly, to determine if a person has previously been infected with SARS-CoV-2. Sources of heterogeneity investigated included: timing of test, test method, SARS-CoV-2 antigen used, test brand, and reference standard for non-SARS-CoV-2 cases. SEARCH METHODS: The COVID-19 Open Access Project living evidence database from the University of Bern (which includes daily updates from PubMed and Embase and preprints from medRxiv and bioRxiv) was searched on 30 September 2020. We included additional publications from the Evidence for Policy and Practice Information and Co-ordinating Centre (EPPI-Centre) 'COVID-19: Living map of the evidence' and the Norwegian Institute of Public Health 'NIPH systematic and living map on COVID-19 evidence'. We did not apply language restrictions. SELECTION CRITERIA: We included test accuracy studies of any design that evaluated commercially produced serology tests, targeting IgG, IgM, IgA alone, or in combination. Studies must have provided data for sensitivity, that could be allocated to a predefined time period after onset of symptoms, or after a positive RT-PCR test. Small studies with fewer than 25 SARS-CoV-2 infection cases were excluded. We included any reference standard to define the presence or absence of SARS-CoV-2 (including reverse transcription polymerase chain reaction tests (RT-PCR), clinical diagnostic criteria, and pre-pandemic samples). DATA COLLECTION AND ANALYSIS: We use standard screening procedures with three reviewers. Quality assessment (using the QUADAS-2 tool) and numeric study results were extracted independently by two people. Other study characteristics were extracted by one reviewer and checked by a second. We present sensitivity and specificity with 95% confidence intervals (CIs) for each test and, for meta-analysis, we fitted univariate random-effects logistic regression models for sensitivity by eligible time period and for specificity by reference standard group. Heterogeneity was investigated by including indicator variables in the random-effects logistic regression models. We tabulated results by test manufacturer and summarised results for tests that were evaluated in 200 or more samples and that met a modification of UK Medicines and Healthcare products Regulatory Agency (MHRA) target performance criteria. MAIN RESULTS: We included 178 separate studies (described in 177 study reports, with 45 as pre-prints) providing 527 test evaluations. The studies included 64,688 samples including 25,724 from people with confirmed SARS-CoV-2; most compared the accuracy of two or more assays (102/178, 57%). Participants with confirmed SARS-CoV-2 infection were most commonly hospital inpatients (78/178, 44%), and pre-pandemic samples were used by 45% (81/178) to estimate specificity. Over two-thirds of studies recruited participants based on known SARS-CoV-2 infection status (123/178, 69%). All studies were conducted prior to the introduction of SARS-CoV-2 vaccines and present data for naturally acquired antibody responses. Seventy-nine percent (141/178) of studies reported sensitivity by week after symptom onset and 66% (117/178) for convalescent phase infection. Studies evaluated enzyme-linked immunosorbent assays (ELISA) (165/527; 31%), chemiluminescent assays (CLIA) (167/527; 32%) or lateral flow assays (LFA) (188/527; 36%). Risk of bias was high because of participant selection (172, 97%); application and interpretation of the index test (35, 20%); weaknesses in the reference standard (38, 21%); and issues related to participant flow and timing (148, 82%). We judged that there were high concerns about the applicability of the evidence related to participants in 170 (96%) studies, and about the applicability of the reference standard in 162 (91%) studies. Average sensitivities for current SARS-CoV-2 infection increased by week after onset for all target antibodies. Average sensitivity for the combination of either IgG or IgM was 41.1% in week one (95% CI 38.1 to 44.2; 103 evaluations; 3881 samples, 1593 cases), 74.9% in week two (95% CI 72.4 to 77.3; 96 evaluations, 3948 samples, 2904 cases) and 88.0% by week three after onset of symptoms (95% CI 86.3 to 89.5; 103 evaluations, 2929 samples, 2571 cases). Average sensitivity during the convalescent phase of infection (up to a maximum of 100 days since onset of symptoms, where reported) was 89.8% for IgG (95% CI 88.5 to 90.9; 253 evaluations, 16,846 samples, 14,183 cases), 92.9% for IgG or IgM combined (95% CI 91.0 to 94.4; 108 evaluations, 3571 samples, 3206 cases) and 94.3% for total antibodies (95% CI 92.8 to 95.5; 58 evaluations, 7063 samples, 6652 cases). Average sensitivities for IgM alone followed a similar pattern but were of a lower test accuracy in every time slot. Average specificities were consistently high and precise, particularly for pre-pandemic samples which provide the least biased estimates of specificity (ranging from 98.6% for IgM to 99.8% for total antibodies). Subgroup analyses suggested small differences in sensitivity and specificity by test technology however heterogeneity in study results, timing of sample collection, and smaller sample numbers in some groups made comparisons difficult. For IgG, CLIAs were the most sensitive (convalescent-phase infection) and specific (pre-pandemic samples) compared to both ELISAs and LFAs (P < 0.001 for differences across test methods). The antigen(s) used (whether from the Spike-protein or nucleocapsid) appeared to have some effect on average sensitivity in the first weeks after onset but there was no clear evidence of an effect during convalescent-phase infection. Investigations of test performance by brand showed considerable variation in sensitivity between tests, and in results between studies evaluating the same test. For tests that were evaluated in 200 or more samples, the lower bound of the 95% CI for sensitivity was 90% or more for only a small number of tests (IgG, n = 5; IgG or IgM, n = 1; total antibodies, n = 4). More test brands met the MHRA minimum criteria for specificity of 98% or above (IgG, n = 16; IgG or IgM, n = 5; total antibodies, n = 7). Seven assays met the specified criteria for both sensitivity and specificity. In a low-prevalence (2%) setting, where antibody testing is used to diagnose COVID-19 in people with symptoms but who have had a negative PCR test, we would anticipate that 1 (1 to 2) case would be missed and 8 (5 to 15) would be falsely positive in 1000 people undergoing IgG or IgM testing in week three after onset of SARS-CoV-2 infection. In a seroprevalence survey, where prevalence of prior infection is 50%, we would anticipate that 51 (46 to 58) cases would be missed and 6 (5 to 7) would be falsely positive in 1000 people having IgG tests during the convalescent phase (21 to 100 days post-symptom onset or post-positive PCR) of SARS-CoV-2 infection. AUTHORS' CONCLUSIONS: Some antibody tests could be a useful diagnostic tool for those in whom molecular- or antigen-based tests have failed to detect the SARS-CoV-2 virus, including in those with ongoing symptoms of acute infection (from week three onwards) or those presenting with post-acute sequelae of COVID-19. However, antibody tests have an increasing likelihood of detecting an immune response to infection as time since onset of infection progresses and have demonstrated adequate performance for detection of prior infection for sero-epidemiological purposes. The applicability of results for detection of vaccination-induced antibodies is uncertain.

Are psychosocial variables, sleep characteristics or central pain processing prognostic factors for outcome following rotator cuff repair? A protocol for a prospective longitudinal cohort study.

INTRODUCTION: Prognosis following surgical rotator cuff repair (RCR) is often established through the assessment of non-modifiable biomedical factors such as tear size. This understates the complex nature of recovery following RCR. There is a need to identify modifiable psychosocial and sleep-related variables, and to find out whether changes in central pain processing influence prognosis after RCR. This will improve our knowledge on how to optimise recovery, using a holistic rehabilitation approach. METHODS AND ANALYSIS: This longitudinal study will analyse 141 participants undergoing usual care for first time RCR. Data will be collected 1-21 days preoperatively (T1), then 11-14 weeks (T2) and 12-14 months (T3) postoperatively. We will use mixed-effects linear regression to assess relationships between potential prognostic factors and our primary and secondary outcome measures-the Western Ontario Rotator Cuff Index; the Constant-Murley Score; the Subjective Shoulder Value; Maximal Pain (Numeric Rating Scale); and Quality of Life (European Quality of Life, 5 dimensions, 5 levels). Potential prognostic factors include: four psychosocial variables; pain catastrophising, perceived stress, injury perceptions and patients' expectations for RCR; sleep; and four factors related to central pain processing (central sensitisation inventory, temporal summation, cold hyperalgesia and pressure pain threshold). Intercorrelations will be assessed to determine the strength of relationships between all potential prognostic indicators.Our aim is to explore whether modifiable psychosocial factors, sleep-related variables and altered central pain processing are associated with outcomes pre-RCR and post-RCR and to identify them as potential prognostic factors. ETHICS AND DISSEMINATION: The results of the study will be disseminated at conferences such as the European Pain Congress. One or more manuscripts will be published in a peer-reviewed SCI-ranked journal. Findings will be reported in accordance with the STROBE statement and PROGRESS framework. Ethical approval is granted by the Ethical commission of Canton of Zurich, Switzerland, No: ID_2018-02089 TRIAL REGISTRATION NUMBER: NCT04946149.

Incidence rates and trends of childhood urinary tract infections and antibiotic prescribing: registry-based study in general practices (2000 to 2020).

BACKGROUND: To improve the management of childhood urinary tract infections, it is essential to understand the incidence rates, testing and treatment strategy. METHODS: A retrospective study using data from 45 to 104 general practices (2000 to 2020) in Flanders (Belgium). We calculated the incidence rates (per 1000 person-years) of cystitis, pyelonephritis, and lab-based urine tests per age (< 2, 2-4, 5-9 and 10-18 years)) and gender in children and performed an autoregressive time-series analysis and seasonality analysis. In children with UTI, we calculated the number of lab-based urine tests and antibiotic prescriptions per person-year and performed an autoregressive time-series analysis. RESULTS: There was a statistically significant increase in the number of UTI episodes from 2000 to 2020 in each age group (p < 0.05), except in boys 2-4 years. Overall, the change in incidence rate was low. In 2020, the incidence rates of cystitis were highest in girls 2-4 years old (40.3 /1000 person-years 95%CI 34.5-46.7) and lowest in boys 10-18 (2.6 /1000 person-years 95%CI 1.8-3.6) The incidence rates of pyelonephritis were highest in girls 2-4 years (5.5, 95%CI 3.5-8.1 /1000 person-years) and children < 2 years of age (boys: 5.4, 95%CI 3.1-8.8 and girls: 4.9, 95%CI 2.7-8.8 /1000 person-years). In children 2-10 years, there was an increase in number of lab-based urine tests per cystitis episode per year and a decrease in total number of electronic antibiotic prescriptions per cystitis episode per year, from 2000 to 2020. In children with cystitis < 10 years in 2020, 51% (95%CI 47-56%) received an electronic antibiotic prescription, of which the majority were broad-spectrum agents. CONCLUSIONS: Over the last 21 years, there was a slight increase in the number of UTI episodes diagnosed in children in Flemish general practices, although the overall change was low. More targeted antibiotic therapy for cystitis in accordance with clinical guidelines is necessary to reduce the use of broad-spectrum agents in children below 10 years.

Signs and symptoms to determine if a patient presenting in primary care or hospital outpatient settings has COVID-19.

BACKGROUND: COVID-19 illness is highly variable, ranging from infection with no symptoms through to pneumonia and life-threatening consequences. Symptoms such as fever, cough, or loss of sense of smell (anosmia) or taste (ageusia), can help flag early on if the disease is present. Such information could be used either to rule out COVID-19 disease, or to identify people who need to go for COVID-19 diagnostic tests. This is the second update of this review, which was first published in 2020. OBJECTIVES: To assess the diagnostic accuracy of signs and symptoms to determine if a person presenting in primary care or to hospital outpatient settings, such as the emergency department or dedicated COVID-19 clinics, has COVID-19. SEARCH METHODS: We undertook electronic searches up to 10 June 2021 in the University of Bern living search database. In addition, we checked repositories of COVID-19 publications. We used artificial intelligence text analysis to conduct an initial classification of documents. We did not apply any language restrictions. SELECTION CRITERIA: Studies were eligible if they included people with clinically suspected COVID-19, or recruited known cases with COVID-19 and also controls without COVID-19 from a single-gate cohort. Studies were eligible when they recruited people presenting to primary care or hospital outpatient settings. Studies that included people who contracted SARS-CoV-2 infection while admitted to hospital were not eligible. The minimum eligible sample size of studies was 10 participants. All signs and symptoms were eligible for this review, including individual signs and symptoms or combinations. We accepted a range of reference standards. DATA COLLECTION AND ANALYSIS: Pairs of review authors independently selected all studies, at both title and abstract, and full-text stage. They resolved any disagreements by discussion with a third review author. Two review authors independently extracted data and assessed risk of bias using the QUADAS-2 checklist, and resolved disagreements by discussion with a third review author. Analyses were restricted to prospective studies only. We presented sensitivity and specificity in paired forest plots, in receiver operating characteristic (ROC) space and in dumbbell plots. We estimated summary parameters using a bivariate random-effects meta-analysis whenever five or more primary prospective studies were available, and whenever heterogeneity across studies was deemed acceptable. MAIN RESULTS: We identified 90 studies; for this update we focused on the results of 42 prospective studies with 52,608 participants. Prevalence of COVID-19 disease varied from 3.7% to 60.6% with a median of 27.4%. Thirty-five studies were set in emergency departments or outpatient test centres (46,878 participants), three in primary care settings (1230 participants), two in a mixed population of in- and outpatients in a paediatric hospital setting (493 participants), and two overlapping studies in nursing homes (4007 participants). The studies did not clearly distinguish mild COVID-19 disease from COVID-19 pneumonia, so we present the results for both conditions together. Twelve studies had a high risk of bias for selection of participants because they used a high level of preselection to decide whether reverse transcription polymerase chain reaction (RT-PCR) testing was needed, or because they enrolled a non-consecutive sample, or because they excluded individuals while they were part of the study base. We rated 36 of the 42 studies as high risk of bias for the index tests because there was little or no detail on how, by whom and when, the symptoms were measured. For most studies, eligibility for testing was dependent on the local case definition and testing criteria that were in effect at the time of the study, meaning most people who were included in studies had already been referred to health services based on the symptoms that we are evaluating in this review. The applicability of the results of this review iteration improved in comparison with the previous reviews. This version has more studies of people presenting to ambulatory settings, which is where the majority of assessments for COVID-19 take place. Only three studies presented any data on children separately, and only one focused specifically on older adults. We found data on 96 symptoms or combinations of signs and symptoms. Evidence on individual signs as diagnostic tests was rarely reported, so this review reports mainly on the diagnostic value of symptoms. Results were highly variable across studies. Most had very low sensitivity and high specificity. RT-PCR was the most often used reference standard (40/42 studies). Only cough (11 studies) had a summary sensitivity above 50% (62.4%, 95% CI 50.6% to 72.9%)); its specificity was low (45.4%, 95% CI 33.5% to 57.9%)). Presence of fever had a sensitivity of 37.6% (95% CI 23.4% to 54.3%) and a specificity of 75.2% (95% CI 56.3% to 87.8%). The summary positive likelihood ratio of cough was 1.14 (95% CI 1.04 to 1.25) and that of fever 1.52 (95% CI 1.10 to 2.10). Sore throat had a summary positive likelihood ratio of 0.814 (95% CI 0.714 to 0.929), which means that its presence increases the probability of having an infectious disease other than COVID-19. Dyspnoea (12 studies) and fatigue (8 studies) had a sensitivity of 23.3% (95% CI 16.4% to 31.9%) and 40.2% (95% CI 19.4% to 65.1%) respectively. Their specificity was 75.7% (95% CI 65.2% to 83.9%) and 73.6% (95% CI 48.4% to 89.3%). The summary positive likelihood ratio of dyspnoea was 0.96 (95% CI 0.83 to 1.11) and that of fatigue 1.52 (95% CI 1.21 to 1.91), which means that the presence of fatigue slightly increases the probability of having COVID-19. Anosmia alone (7 studies), ageusia alone (5 studies), and anosmia or ageusia (6 studies) had summary sensitivities below 50% but summary specificities over 90%. Anosmia had a summary sensitivity of 26.4% (95% CI 13.8% to 44.6%) and a specificity of 94.2% (95% CI 90.6% to 96.5%). Ageusia had a summary sensitivity of 23.2% (95% CI 10.6% to 43.3%) and a specificity of 92.6% (95% CI 83.1% to 97.0%). Anosmia or ageusia had a summary sensitivity of 39.2% (95% CI 26.5% to 53.6%) and a specificity of 92.1% (95% CI 84.5% to 96.2%). The summary positive likelihood ratios of anosmia alone and anosmia or ageusia were 4.55 (95% CI 3.46 to 5.97) and 4.99 (95% CI 3.22 to 7.75) respectively, which is just below our arbitrary definition of a 'red flag', that is, a positive likelihood ratio of at least 5. The summary positive likelihood ratio of ageusia alone was 3.14 (95% CI 1.79 to 5.51). Twenty-four studies assessed combinations of different signs and symptoms, mostly combining olfactory symptoms. By combining symptoms with other information such as contact or travel history, age, gender, and a local recent case detection rate, some multivariable prediction scores reached a sensitivity as high as 90%. AUTHORS' CONCLUSIONS: Most individual symptoms included in this review have poor diagnostic accuracy. Neither absence nor presence of symptoms are accurate enough to rule in or rule out the disease. The presence of anosmia or ageusia may be useful as a red flag for the presence of COVID-19. The presence of cough also supports further testing. There is currently no evidence to support further testing with PCR in any individuals presenting only with upper respiratory symptoms such as sore throat, coryza or rhinorrhoea. Combinations of symptoms with other readily available information such as contact or travel history, or the local recent case detection rate may prove more useful and should be further investigated in an unselected population presenting to primary care or hospital outpatient settings. The diagnostic accuracy of symptoms for COVID-19 is moderate to low and any testing strategy using symptoms as selection mechanism will result in both large numbers of missed cases and large numbers of people requiring testing. Which one of these is minimised, is determined by the goal of COVID-19 testing strategies, that is, controlling the epidemic by isolating every possible case versus identifying those with clinically important disease so that they can be monitored or treated to optimise their prognosis. The former will require a testing strategy that uses very few symptoms as entry criterion for testing, the latter could focus on more specific symptoms such as fever and anosmia.

Diagnostic value of biomarkers for paediatric urinary tract infections in primary care: systematic review and meta-analysis.

BACKGROUND: Accurate diagnosis of urinary tract infection is essential as children left untreated may suffer permanent renal injury. AIM: To compare the diagnostic values of biomarkers or clinical prediction rules for urinary tract infections in children presenting to ambulatory care. DESIGN AND SETTING: Systematic review and meta-analysis of ambulatory care studies. METHODS: Medline, Embase, WOS, CINAHL, Cochrane library, HTA and DARE were searched until 21 May 2021. We included diagnostic studies on urine or blood biomarkers for cystitis or pyelonephritis in children below 18 years of age. We calculated sensitivity, specificity and likelihood ratios. Data were pooled using a bivariate random effects model and a Hierarchical Summary Receiver Operating Characteristic analysis. RESULTS: Seventy-five moderate to high quality studies were included in this review and 54 articles in the meta-analyses. The area under the receiver-operating-characteristics curve to diagnose cystitis was 0.75 (95%CI 0.62 to 0.83, n = 9) for C-reactive protein, 0.71 (95% CI 0.62 to 0.80, n = 4) for procalcitonin, 0.93 (95% CI 0.91 to 0.96, n = 22) for the dipstick test (nitrite or leukocyte esterase ≥trace), 0.94 (95% CI 0.58 to 0.98, n = 9) for urine white blood cells and 0.98 (95% CI 0.92 to 0.99, n = 12) for Gram-stained bacteria. For pyelonephritis, C-reactive protein < 20 mg/l had LR- of 0.10 (95%CI 0.04-0.30) to 0.22 (95%CI 0.09-0.54) in children with signs suggestive of urinary tract infection. CONCLUSIONS: Clinical prediction rules including the dipstick test biomarkers can support family physicians while awaiting urine culture results. CRP and PCT have low accuracy for cystitis, but might be useful for pyelonephritis.

Clinical Features for the Diagnosis of Pediatric Urinary Tract Infections: Systematic Review and Meta-Analysis.

PURPOSE: Accurate diagnosis of urinary tract infection in children is essential because children left untreated can experience permanent renal injury. We aimed to assess the diagnostic value of clinical features of pediatric urinary tract infection. METHODS: We performed a systematic review and meta-analysis of diagnostic test accuracy studies in ambulatory care. We searched the PubMed, Embase, Web of Science, Cumulative Index to Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials, Health Technology Assessment, and Database of Abstracts of Reviews of Effects databases from inception to January 27, 2020 for studies reporting 2 × 2 diagnostic accuracy data for clinical features compared with urine culture in children aged <18 years. For each clinical feature, we calculated likelihood ratios and posttest probabilities of urinary tract infection. To estimate summary parameters, we conducted a bivariate random effects meta-analysis and hierarchical summary receiver operating characteristic analysis. RESULTS: A total of 35 studies (N = 78,427 patients) of moderate to high quality were included, providing information on 58 clinical features and 6 prediction rules. Only circumcision (negative likelihood ratio [LR-] 0.24; 95% CI, 0.08-0.72; n = 8), stridor (LR- 0.20; 95% CI, 0.05-0.81; n = 1), and diaper rash (LR- 0.13; 95% CI, 0.02-0.92; n = 1) were useful for ruling out urinary tract infection. Body temperature or fever duration showed limited diagnostic value (area under the receiver operating characteristic curve 0.61; 95% CI, 0.47-0.73; n = 16). The Diagnosis of Urinary Tract Infection in Young Children score, Gorelick Scale score, and UTIcalc (https://uticalc.pitt.edu) might be useful to identify children eligible for urine sampling. CONCLUSIONS: Few clinical signs and symptoms are useful for diagnosing or ruling out urinary tract infection in children. Clinical prediction rules might be more accurate; however, they should be validated externally. Physicians should not restrict urine sampling to children with unexplained fever or other features suggestive of urinary tract infection.

Signs and symptoms to determine if a patient presenting in primary care or hospital outpatient settings has COVID-19.

BACKGROUND: The clinical implications of SARS-CoV-2 infection are highly variable. Some people with SARS-CoV-2 infection remain asymptomatic, whilst the infection can cause mild to moderate COVID-19 and COVID-19 pneumonia in others. This can lead to some people requiring intensive care support and, in some cases, to death, especially in older adults. Symptoms such as fever, cough, or loss of smell or taste, and signs such as oxygen saturation are the first and most readily available diagnostic information. Such information could be used to either rule out COVID-19, or select patients for further testing. This is an update of this review, the first version of which published in July 2020. OBJECTIVES: To assess the diagnostic accuracy of signs and symptoms to determine if a person presenting in primary care or to hospital outpatient settings, such as the emergency department or dedicated COVID-19 clinics, has COVID-19. SEARCH METHODS: For this review iteration we undertook electronic searches up to 15 July 2020 in the Cochrane COVID-19 Study Register and the University of Bern living search database. In addition, we checked repositories of COVID-19 publications. We did not apply any language restrictions. SELECTION CRITERIA: Studies were eligible if they included patients with clinically suspected COVID-19, or if they recruited known cases with COVID-19 and controls without COVID-19. Studies were eligible when they recruited patients presenting to primary care or hospital outpatient settings. Studies in hospitalised patients were only included if symptoms and signs were recorded on admission or at presentation. Studies including patients who contracted SARS-CoV-2 infection while admitted to hospital were not eligible. The minimum eligible sample size of studies was 10 participants. All signs and symptoms were eligible for this review, including individual signs and symptoms or combinations. We accepted a range of reference standards. DATA COLLECTION AND ANALYSIS: Pairs of review authors independently selected all studies, at both title and abstract stage and full-text stage. They resolved any disagreements by discussion with a third review author. Two review authors independently extracted data and resolved disagreements by discussion with a third review author. Two review authors independently assessed risk of bias using the Quality Assessment tool for Diagnostic Accuracy Studies (QUADAS-2) checklist. We presented sensitivity and specificity in paired forest plots, in receiver operating characteristic space and in dumbbell plots. We estimated summary parameters using a bivariate random-effects meta-analysis whenever five or more primary studies were available, and whenever heterogeneity across studies was deemed acceptable. MAIN RESULTS: We identified 44 studies including 26,884 participants in total. Prevalence of COVID-19 varied from 3% to 71% with a median of 21%. There were three studies from primary care settings (1824 participants), nine studies from outpatient testing centres (10,717 participants), 12 studies performed in hospital outpatient wards (5061 participants), seven studies in hospitalised patients (1048 participants), 10 studies in the emergency department (3173 participants), and three studies in which the setting was not specified (5061 participants). The studies did not clearly distinguish mild from severe COVID-19, so we present the results for all disease severities together. Fifteen studies had a high risk of bias for selection of participants because inclusion in the studies depended on the applicable testing and referral protocols, which included many of the signs and symptoms under study in this review. This may have especially influenced the sensitivity of those features used in referral protocols, such as fever and cough. Five studies only included participants with pneumonia on imaging, suggesting that this is a highly selected population. In an additional 12 studies, we were unable to assess the risk for selection bias. This makes it very difficult to judge the validity of the diagnostic accuracy of the signs and symptoms from these included studies. The applicability of the results of this review update improved in comparison with the original review. A greater proportion of studies included participants who presented to outpatient settings, which is where the majority of clinical assessments for COVID-19 take place. However, still none of the studies presented any data on children separately, and only one focused specifically on older adults. We found data on 84 signs and symptoms. Results were highly variable across studies. Most had very low sensitivity and high specificity. Only cough (25 studies) and fever (7 studies) had a pooled sensitivity of at least 50% but specificities were moderate to low. Cough had a sensitivity of 67.4% (95% confidence interval (CI) 59.8% to 74.1%) and specificity of 35.0% (95% CI 28.7% to 41.9%). Fever had a sensitivity of 53.8% (95% CI 35.0% to 71.7%) and a specificity of 67.4% (95% CI 53.3% to 78.9%). The pooled positive likelihood ratio of cough was only 1.04 (95% CI 0.97 to 1.11) and that of fever 1.65 (95% CI 1.41 to 1.93). Anosmia alone (11 studies), ageusia alone (6 studies), and anosmia or ageusia (6 studies) had sensitivities below 50% but specificities over 90%. Anosmia had a pooled sensitivity of 28.0% (95% CI 17.7% to 41.3%) and a specificity of 93.4% (95% CI 88.3% to 96.4%). Ageusia had a pooled sensitivity of 24.8% (95% CI 12.4% to 43.5%) and a specificity of 91.4% (95% CI 81.3% to 96.3%). Anosmia or ageusia had a pooled sensitivity of 41.0% (95% CI 27.0% to 56.6%) and a specificity of 90.5% (95% CI 81.2% to 95.4%). The pooled positive likelihood ratios of anosmia alone and anosmia or ageusia were 4.25 (95% CI 3.17 to 5.71) and 4.31 (95% CI 3.00 to 6.18) respectively, which is just below our arbitrary definition of a 'red flag', that is, a positive likelihood ratio of at least 5. The pooled positive likelihood ratio of ageusia alone was only 2.88 (95% CI 2.02 to 4.09). Only two studies assessed combinations of different signs and symptoms, mostly combining fever and cough with other symptoms. These combinations had a specificity above 80%, but at the cost of very low sensitivity (< 30%). AUTHORS' CONCLUSIONS: The majority of individual signs and symptoms included in this review appear to have very poor diagnostic accuracy, although this should be interpreted in the context of selection bias and heterogeneity between studies. Based on currently available data, neither absence nor presence of signs or symptoms are accurate enough to rule in or rule out COVID-19. The presence of anosmia or ageusia may be useful as a red flag for COVID-19. The presence of fever or cough, given their high sensitivities, may also be useful to identify people for further testing. Prospective studies in an unselected population presenting to primary care or hospital outpatient settings, examining combinations of signs and symptoms to evaluate the syndromic presentation of COVID-19, are still urgently needed. Results from such studies could inform subsequent management decisions.

Burden of infections on older patients presenting to general practice: a registry-based study.

BACKGROUND: Estimates on the incidence rates of infections are needed to assess the burden of disease in the community. OBJECTIVE: To assess incidence rates of potentially serious infections in patients aged 65 years and over presenting to Flemish general practice from 2000 to 2015, and to describe patient characteristics. METHODS: We performed a retrospective study, based on data provided by the Intego morbidity registry of the KU Leuven, which includes the electronic medical records of 111 general practitioners. Incidence rates were calculated taking person-time at risk into account, and longitudinal trends from 2000 to 2015 were analysed using autoregressive time-series analyses. RESULTS: On average, a person aged 65 years or older has an 8.0% risk of getting a potentially serious infection each year. Acute cystitis was the most often occurring potentially serious infection [39.8/1000 person-years; 95% confidence interval (CI): 39.4-40.2], followed by influenza like illness (ILI, 24.3/1000 person-years; 95% CI: 24.0-24.6) and pneumonia (9.7/1000 person-years; 95% CI: 9.5-9.9). The incidence rates of pneumonia were higher in older age groups and in men, whereas they were markedly lower for ILI at older ages, in both genders. From 2000 to 2015, overall incidence rates decreased significantly for ILI, while they increased in women for pneumonia, acute cystitis and pyelonephritis. Common chronic comorbidities were non-insulin dependent diabetes, chronic obstructive pulmonary disease, asthma, heart failure and chronic renal insufficiency. CONCLUSIONS: Potentially serious infections are quite common in an older patient population presenting to primary care. They are accompanied by several chronic comorbidities, which may differ by infection type.

Diagnosing serious infections in older adults presenting to ambulatory care: a systematic review.

OBJECTIVES: to summarise all available evidence on the accuracy of clinical features and blood tests for diagnosing serious infections in older patients presenting to ambulatory care. METHODS: systematic review, searching seven databases using a comprehensive search strategy. We included cross-sectional prospective diagnostic studies on (1) clinical features, (2) diagnostic prediction rules based on clinical features alone, (3) blood tests and (4) diagnostic prediction rules combining clinical features and blood tests. Study participants had to be community-dwelling adults aged ≥65 years, in whom a physician suspected an infection. We used QUADAS-2 to assess risk of bias. We calculated measures of diagnostic accuracy and present descriptive statistics. RESULTS: out of 13,757 unique articles, only six studies with a moderate to high risk of bias were included. There was substantial clinical heterogeneity across these studies. Clinical features had LR- ≥0.61 and LR+ ≤4.94. Twelve prediction rules using clinical features had LR- ≥0.30 and LR+ ≤2.78. There was evidence on four blood tests of which procalcitonin was the most often investigated: levels <0.37 ng/ml (LR- = 0.20; 95%CI 0.10-0.42) were suitable to rule out sepsis in moderately high prevalence situations. Two diagnostic prediction rules combining clinical features and procalcitonin had LR- of ≤0.12 (95%CI 0.05-0.33) and LR+ of maximum 1.39 (95%CI 1.30-1.49). CONCLUSIONS: we found few studies on the diagnostic accuracy of clinical features and blood tests to detect serious infections in older people presenting to ambulatory care. The risk of bias was mostly moderate to high, leading to substantial uncertainty.

Prediction of Shoulder Pain in Youth Competitive Swimmers: The Development and Internal Validation of a Prognostic Prediction Model.

BACKGROUND: Knowledge of predictors for shoulder pain in swimmers can assist professionals working with the athlete in developing optimal prevention strategies. However, study methodology and limited available data have constrained a comprehensive understanding of which factors cause shoulder pain. PURPOSE: To investigate risk factors and develop and internally validate a multivariable prognostic model for the prediction of shoulder pain in swimmers. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: A total of 201 pain-free club- to international-level competitive swimmers were followed for 2 consecutive seasons. The cohort consisted of 96 male (mean ± SD age, 13.9 ± 2.2 years) and 105 female (13.9 ± 2.2 years) swimmers. Demographic, sport-specific, and musculoskeletal characteristics were assessed every 6 months. Swim-training exposure was observed prospectively. Shoulder pain interfering with training was the primary outcome. Multiple imputation was used to cope with missing data. The final model was estimated using multivariable logistic regression. We applied bootstrapping to internally validate the model and correct for overoptimism. RESULTS: A total of 42 new cases of shoulder pain were recorded during the study. Average duration of follow-up was 1.1 years. Predictors included in the final model were acute:chronic workload ratio (odds ratio [OR], 4.31; 95% CI, 1.00-18.54), competitive level (OR, 0.19; 95% CI, 0.06-0.63), shoulder flexion range of motion, posterior shoulder muscle endurance (OR, 0.96; 95% CI, 0.92-0.99), and hand entry position error (OR, 0.37; 95% CI, 0.16-0.91). After internal validation, this model maintained good calibration and discriminative power (area under the receiver operating characteristic curve, 0.71; 95% CI, 0.60-0.94). CONCLUSION: Our model consists of parameters that are readily measurable in a swimming setting, allowing the identification of swimmers at risk for shoulder pain. Multivariable logistic regression showed the strongest predictors for shoulder pain were regional competitive swimming level, acute:chronic workload ratio, posterior shoulder muscle endurance, and hand entry error.

Signs and symptoms to determine if a patient presenting in primary care or hospital outpatient settings has COVID-19 disease.

BACKGROUND: Some people with SARS-CoV-2 infection remain asymptomatic, whilst in others the infection can cause mild to moderate COVID-19 disease and COVID-19 pneumonia, leading some patients to require intensive care support and, in some cases, to death, especially in older adults. Symptoms such as fever or cough, and signs such as oxygen saturation or lung auscultation findings, are the first and most readily available diagnostic information. Such information could be used to either rule out COVID-19 disease, or select patients for further diagnostic testing. OBJECTIVES: To assess the diagnostic accuracy of signs and symptoms to determine if a person presenting in primary care or to hospital outpatient settings, such as the emergency department or dedicated COVID-19 clinics, has COVID-19 disease or COVID-19 pneumonia. SEARCH METHODS: On 27 April 2020, we undertook electronic searches in the Cochrane COVID-19 Study Register and the University of Bern living search database, which is updated daily with published articles from PubMed and Embase and with preprints from medRxiv and bioRxiv. In addition, we checked repositories of COVID-19 publications. We did not apply any language restrictions. SELECTION CRITERIA: Studies were eligible if they included patients with suspected COVID-19 disease, or if they recruited known cases with COVID-19 disease and controls without COVID-19. Studies were eligible when they recruited patients presenting to primary care or hospital outpatient settings. Studies including patients who contracted SARS-CoV-2 infection while admitted to hospital were not eligible. The minimum eligible sample size of studies was 10 participants. All signs and symptoms were eligible for this review, including individual signs and symptoms or combinations. We accepted a range of reference standards including reverse transcription polymerase chain reaction (RT-PCR), clinical expertise, imaging, serology tests and World Health Organization (WHO) or other definitions of COVID-19. DATA COLLECTION AND ANALYSIS: Pairs of review authors independently selected all studies, at both title and abstract stage and full-text stage. They resolved any disagreements by discussion with a third review author. Two review authors independently extracted data and resolved disagreements by discussion with a third review author. Two review authors independently assessed risk of bias using the QUADAS-2 checklist. Analyses were descriptive, presenting sensitivity and specificity in paired forest plots, in ROC (receiver operating characteristic) space and in dumbbell plots. We did not attempt meta-analysis due to the small number of studies, heterogeneity across studies and the high risk of bias. MAIN RESULTS: We identified 16 studies including 7706 participants in total. Prevalence of COVID-19 disease varied from 5% to 38% with a median of 17%. There were no studies from primary care settings, although we did find seven studies in outpatient clinics (2172 participants), and four studies in the emergency department (1401 participants). We found data on 27 signs and symptoms, which fall into four different categories: systemic, respiratory, gastrointestinal and cardiovascular. No studies assessed combinations of different signs and symptoms and results were highly variable across studies. Most had very low sensitivity and high specificity; only six symptoms had a sensitivity of at least 50% in at least one study: cough, sore throat, fever, myalgia or arthralgia, fatigue, and headache. Of these, fever, myalgia or arthralgia, fatigue, and headache could be considered red flags (defined as having a positive likelihood ratio of at least 5) for COVID-19 as their specificity was above 90%, meaning that they substantially increase the likelihood of COVID-19 disease when present. Seven studies carried a high risk of bias for selection of participants because inclusion in the studies depended on the applicable testing and referral protocols, which included many of the signs and symptoms under study in this review. Five studies only included participants with pneumonia on imaging, suggesting that this is a highly selected population. In an additional four studies, we were unable to assess the risk for selection bias. These factors make it very difficult to determine the diagnostic properties of these signs and symptoms from the included studies. We also had concerns about the applicability of these results, since most studies included participants who were already admitted to hospital or presenting to hospital settings. This makes these findings less applicable to people presenting to primary care, who may have less severe illness and a lower prevalence of COVID-19 disease. None of the studies included any data on children, and only one focused specifically on older adults. We hope that future updates of this review will be able to provide more information about the diagnostic properties of signs and symptoms in different settings and age groups. AUTHORS' CONCLUSIONS: The individual signs and symptoms included in this review appear to have very poor diagnostic properties, although this should be interpreted in the context of selection bias and heterogeneity between studies. Based on currently available data, neither absence nor presence of signs or symptoms are accurate enough to rule in or rule out disease. Prospective studies in an unselected population presenting to primary care or hospital outpatient settings, examining combinations of signs and symptoms to evaluate the syndromic presentation of COVID-19 disease, are urgently needed. Results from such studies could inform subsequent management decisions such as self-isolation or selecting patients for further diagnostic testing. We also need data on potentially more specific symptoms such as loss of sense of smell. Studies in older adults are especially important.

International Consensus Definition of a Serious Infection in a Geriatric Patient Presenting to Ambulatory Care.

Early recognition and prompt treatment of a serious infection is important to optimize prognosis in older patients. The current evidence base underpinning this early recognition in ambulatory care is scattered and haphazard, calling for new research to strengthen clinical practice. Before embarking on such studies, it is important to seek consensus on what constitutes a serious infection in older patients presenting to ambulatory care. We conducted a 4-round e-Delphi study seeking consensus among medical professionals who deliver clinical care to older patients using online questionnaires and feedback. Twenty-two specialists in emergency care, general practice, geriatrics, and infectious diseases from 10 different countries participated in our study. We constructed 18 statements from the answers to the open questions in round 1, which were then rated by the participants in 2 consecutive rounds. After assessing the level of agreement, consensus, and stability, the following definition was preferred by 94% of the participants: "A serious infection in a geriatric patient presenting to ambulatory care is an infection with a high risk of complications, functional decline, and/or mortality, requiring a prompt diagnostic and therapeutic approach in the appropriate care setting. The most important determinants of the choice of setting are the level of emergency, the geriatric profile of the patient (frailty status, functional status, and comorbidities), and the patients' level of autonomy and personal preferences. Factors such as the feasibility of home care, the potential consequences of delayed or suboptimal treatment and infection specific treatment requirements should be weighed as well when choosing the appropriate care setting." Based on consensus among 22 clinicians working in 10 different countries, we propose a definition for serious infections in geriatric patients presenting to ambulatory care. This will form the basis of future studies in this domain.

Intrarater and Interrater Reliability of a Passive Shoulder Flexion Range of Motion Measurement for Latissimus Dorsi Flexibility in Young Competitive Swimmers.

CONTEXT: The latissimus dorsi plays a major role in generating the propulsive force during swimming. In addition, stiffness of this muscle may result in altered stroke biomechanics and predispose swimmers to shoulder pain. Measuring the flexibility of the latissimus dorsi can be of interest to reduce injury. However, the reliability of such measurement has not yet been investigated in competitive swimmers. OBJECTIVE: To assess the within-session intrarater and interrater reliability of a passive shoulder flexion range of motion measurement for latissimus dorsi flexibility in competitive swimmers. DESIGN: Within-session intrarater and interrater reliability. SETTING: Competitive swimming clubs in Flanders, Belgium. PARTICIPANTS: Twenty-six competitive swimmers (15.46 [2.98] y; 16 men and 10 women). INTERVENTION: Each rater performed 2 alternating (eg, left-right-left-right) measurements of passive shoulder flexion range of motion twice, with a 30-second rest period in between. MAIN OUTCOME MEASURES: The intraclass correlation coefficients were calculated to assess intrarater and interrater reliability. RESULTS: Interrater intraclass correlation coefficient ranged from .54 (95% confidence interval [CI], -.16 to .81) to .57 (95% CI, -.24 to .85). Results for the intrarater reliability ranged from .91 (95% CI, .81 to .96) to .94 (95% CI, .87 to .97). CONCLUSION: Results of this study suggest that shoulder flexion range of motion in young competitive swimmers can be measured reliably by a single rater within the same session.

The effect of HIV infection and exposure on cognitive development in the first two years of life in Malawi.

OBJECTIVES: To assess longitudinal patterns and determinants of cognitive development in infants living with HIV, infants exposed to maternal HIV infection, and HIV-unexposed infants. METHODS: Prospective, community-based cohort study of 555 Malawian infants aged 8 weeks to 24 months, using multivariable linear mixed-effects regression models with random intercepts to analyze repeated measures of cognitive function. RESULTS: At 3 months of age, cognitive scores on the Bayley Scales of Infant Development (BSID 3rd edition) were lower in the 96 HIV-infected infants (mean = 14.1 (SD:4.8)) compared to the 289 HIV-exposed (mean = 16.5 (SD:3.7)) and the 170 unexposed infants (mean = 17.5 (SD:3.3)). Over the first two years of life, the small deficit in cognitive development of infants living with HIV who survived and remained in care did not increase (mean score 52.9 among HIV-infected vs 55.6 among HIV unexposed). In multivariable analysis, malnutrition and a more advanced clinical infant HIV stage had a negative impact on cognition at age 3, while financial security, care by the biological mother, and ART for mother and child were associated with better cognitive status at this young age. The positive influence of maternal ART reversed with age. CONCLUSIONS: Malawian infants exposed to HIV had a cognitive development that was similar to their unexposed peers in the first two years of life, while that of HIV infected infants lagged behind from the start. Early initiation of effective ART in all HIV infected mothers and infants, and prevention of infant malnutrition are important to safeguard cognitive development of children affected by HIV.

Antimicrobial prescribing by Belgian dentists in ambulatory care, from 2010 to 2016.

OBJECTIVES: To describe antimicrobial prescribing by Belgian dentists in ambulatory care, from 2010 until 2016. MATERIALS AND METHODS: Reimbursement data from the Belgian National Institute for Health and Disability Insurance were analysed to evaluate antimicrobial prescribing (WHO ATC-codes J01/P01AB). Utilisation was expressed in defined daily doses (DDDs), and in DDDs and packages per 1000 inhabitants per day (DID and PID, respectively). Additionally, the number of DDD and packages per prescriber was calculated. RESULTS: In 2016, the dentistry-related prescribing rate of 'Antibacterials for systemic use' (J01) and 'Antiprotozoals' (P01AB) was 1.607 and 0.014 DID, respectively. From 2010 to 2016, the DID rate of J01 increased by 6.3%, while the PID rate declined by 6.7%. Amoxicillin and amoxicillin with an enzyme inhibitor were the most often prescribed products, followed by clindamycin, clarithromycin, doxycycline, azithromycin and metronidazole. The proportion of amoxicillin relative to amoxicillin with an enzyme inhibitor was low. The narrow-spectrum antibiotic penicillin V was almost never prescribed. CONCLUSIONS: Antibiotics typically classified as broad- or extended-spectrum were prescribed most often by Belgian dentists during the period 2000-2016. Although the DID rate of all 'Antibacterials for systemic use' (J01) increased over the years, the number of prescriptions per dentist decreased since 2013. The high prescription level of amoxicillin with an enzyme inhibitor is particularly worrying. It indicates that there is a need for comprehensive clinical practice guidelines for Belgian dentists.

Intra- and interrater reliability of the 'lumbar-locked thoracic rotation test' in competitive swimmers ages 10 through 18 years.

OBJECTIVES: Measuring thoracic spine mobility can be of interest to competitive swimmers as it has been associated with shoulder girdle function and scapular position in subjects with and without shoulder pain. At present, no reliability data of thoracic spine mobility measurements are available in the swimming population. This study aims to evaluate the within-session intra- and interrater reliability of the "lumbar-locked rotation test" for thoracic spine rotation in competitive swimmers aged 10 to 18 years. This reliability study is part of a larger prospective cohort study investigating potential risk factors for the development of shoulder pain in competitive swimmers. DESIGN: Within-session, intra- and inter-rater reliability. SETTING: Competitive swimming clubs in Belgium. PARTICIPANTS: 21 competitive swimmers. MAIN OUTCOME MEASURES: Intra- and inter-rater reliability of the lumbar-locked thoracic rotation test. RESULTS: Intraclass correlation coefficients (ICCs) ranged from 0.91 (95% CI 0.78 to 0.96) to 0.96 (0.89-0.98) for intra-rater reliability. Results for inter-rater reliability ranged from 0.89 (0.72-0.95) to 0.86 (0.65-0.94) respectively for right and left thoracic rotation. CONCLUSION: Results suggest good to excellent reliability of the lumbar-locked thoracic rotation test, indicating this test can be used reliably in clinical practice.