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Background Updatable estimates of COVID-19 onset, progression, and trajectories underpin pandemic mitigation efforts. To identify and characterise disease trajectories, we aimed to define and validate ten COVID-19 phenotypes from nationwide linked electronic health records (EHR) using an extensible framework. Methods In this cohort study, we used eight linked National Health Service (NHS) datasets for people in England alive on Jan 23, 2020. Data on COVID-19 testing, vaccination, primary and secondary care records, and death registrations were collected until Nov 30, 2021. We defined ten COVID-19 phenotypes reflecting clinically relevant stages of disease severity and encompassing five categories: positive SARS-CoV-2 test, primary care diagnosis, hospital admission, ventilation modality (four phenotypes), and death (three phenotypes). We constructed patient trajectories illustrating transition frequency and duration between phenotypes. Analyses were stratified by pandemic waves and vaccination status. Findings Among 57 032 174 individuals included in the cohort, 13 990 423 COVID-19 events were identified in 7 244 925 individuals, equating to an infection rate of 12·7% during the study period. Of 7 244 925 individuals, 460 737 (6·4%) were admitted to hospital and 158 020 (2·2%) died. Of 460 737 individuals who were admitted to hospital, 48 847 (10·6%) were admitted to the intensive care unit (ICU), 69 090 (15·0%) received non-invasive ventilation, and 25 928 (5·6%) received invasive ventilation. Among 384 135 patients who were admitted to hospital but did not require ventilation, mortality was higher in wave 1 (23 485 [30·4%] of 77 202 patients) than wave 2 (44 220 [23·1%] of 191 528 patients), but remained unchanged for patients admitted to the ICU. Mortality was highest among patients who received ventilatory support outside of the ICU in wave 1 (2569 [50·7%] of 5063 patients). 15 486 (9·8%) of 158 020 COVID-19-related deaths occurred within 28 days of the first COVID-19 event without a COVID-19 diagnoses on the death certificate. 10 884 (6·9%) of 158 020 deaths were identified exclusively from mortality data with no previous COVID-19 phenotype recorded. We observed longer patient trajectories in wave 2 than wave 1. Interpretation Our analyses illustrate the wide spectrum of disease trajectories as shown by differences in incidence, survival, and clinical pathways. We have provided a modular analytical framework that can be used to monitor the impact of the pandemic and generate evidence of clinical and policy relevance using multiple EHR sources. Funding British Heart Foundation Data Science Centre, led by Health Data Research UK.

Background Health professionals sometimes do not use the best evidence to treat their patients, in part due to unconscious acts of omission and information overload. Reminders help clinicians overcome these problems by prompting them to recall information that they already know, or by presenting information in a different and more accessible format. Manually-generated reminders delivered on paper are defined as information given to the health professional with each patient or encounter, provided on paper, in which no computer is involved in the production or delivery of the reminder. Manually-generated reminders delivered on paper are relatively cheap interventions, and are especially relevant in settings where electronic clinical records are not widely available and affordable. This review is one of three Cochrane Reviews focused on the effectiveness of reminders in health care. Objectives 1. To determine the effectiveness of manually-generated reminders delivered on paper in changing professional practice and improving patient outcomes. 2. To explore whether a number of potential effect modifiers influence the effectiveness of manually-generated reminders delivered on paper. Search methods We searched CENTRAL, MEDLINE, Embase, CINAHL and two trials registers on 5 December 2018. We searched grey literature, screened individual journals, conference proceedings and relevant systematic reviews, and reviewed reference lists and cited references of included studies. Selection criteria We included randomised and non-randomised trials assessing the impact of manually-generated reminders delivered on paper as a single intervention (compared with usual care) or added to one or more co-interventions as a multicomponent intervention (compared with the co-intervention(s) without the reminder component) on professional practice or patients' outcomes. We also included randomised and non-randomised trials comparing manually-generated reminders with other quality improvement (QI) interventions. Data collection and analysis Two review authors screened studies for eligibility and abstracted data independently. We extracted the primary outcome as defined by the authors or calculated the median effect size across all reported outcomes in each study. We then calculated the median percentage improvement and interquartile range across the included studies that reported improvement related outcomes, and assessed the certainty of the evidence using the GRADE approach. Main results We identified 63 studies (41 cluster-randomised trials, 18 individual randomised trials, and four non-randomised trials) that met all inclusion criteria. Fifty-seven studies reported usable data (64 comparisons). The studies were mainly located in North America (42 studies) and the UK (eight studies). Fifty-four studies took place in outpatient/ambulatory settings. The clinical areas most commonly targeted were cardiovascular disease management (11 studies), cancer screening (10 studies) and preventive care (10 studies), and most studies had physicians as their target population (57 studies). General management of a clinical condition (17 studies), test-ordering (14 studies) and prescription (10 studies) were the behaviours more commonly targeted by the intervention. Forty-eight studies reported changes in professional practice measured as dichotomous process adherence outcomes (e.g. compliance with guidelines recommendations), 16 reported those changes measured as continuous process-of-care outcomes (e.g. number of days with catheters), eight reported dichotomous patient outcomes (e.g. mortality rates) and five reported continuous patient outcomes (e.g. mean systolic blood pressure). Manually-generated reminders delivered on paper probably improve professional practice measured as dichotomous process adherence outcomes) compared with usual care (median improvement 8.45% (IQR 2.54% to 20.58%); 39 comparisons, 40,346 participants; moderate certainty of evidence) and may make little or no difference to continuous process-of-care outcomes (8 comparisons, 3263 participants; low certainty of evidence). Adding manually-generated paper reminders to one or more QI co-interventions may slightly improve professional practice measured as dichotomous process adherence outcomes (median improvement 4.24% (IQR -1.09% to 5.50%); 12 comparisons, 25,359 participants; low certainty of evidence) and probably slightly improve professional practice measured as continuous outcomes (median improvement 0.28 (IQR 0.04 to 0.51); 2 comparisons, 12,372 participants; moderate certainty of evidence). Compared with other QI interventions, manually-generated reminders may slightly decrease professional practice measured as process adherence outcomes (median decrease 7.9% (IQR -0.7% to 11%); 14 comparisons, 21,274 participants; low certainty of evidence). We are uncertain whether manually-generated reminders delivered on paper, compared with usual care or with other QI intervention, lead to better or worse patient outcomes (dichotomous or continuous), as the certainty of the evidence is very low (10 studies, 13 comparisons). Reminders added to other QI interventions may make little or no difference to patient outcomes (dichotomous or continuous) compared with the QI alone (2 studies, 2 comparisons). Regarding resource use, studies reported additional costs per additional point of effectiveness gained, but because of the different currencies and years used the relevance of those figures is uncertain. None of the included studies reported outcomes related to harms or adverse effects. Authors' conclusions Manually-generated reminders delivered on paper as a single intervention probably lead to small to moderate increases in outcomes related to adherence to clinical recommendations, and they could be used as a single QI intervention. It is uncertain whether reminders should be added to other QI intervention already in place in the health system, although the effects may be positive. If other QI interventions, such as patient or computerised reminders, are available, they should be preferred over manually-generated reminders, but under close evaluation in order to decrease uncertainty about their potential effect.

Mortality rates for cervical cancer (CC) in Chile are higher than those of developed countries and it has an unequal socioeconomic distribution. The recognition of human papilloma virus (HPV) as the causal agent of cervical cancer in the early 80’s changed the prevention paradigms. Current goals are to prevent HPV infection by vaccination before the onset of sexual activity and to detect HPV infection in women older than 30 years. This article reviews CC prevention and early detection methods, discusses relevant evidence to support a change in Chile and presents an innovation proposal. A strategy of primary screening based on HPV detection followed by triage of HPV-positive women by colposcopy in primary care or by cytological or molecular reflex testing is proposed. Due to the existence in Chile of a well-organized nationwide CC prevention program, the replacement of a low-sensitivity screening test such as the Papanicolau test with a highly sensitive one such as HPV detection, could quickly improve the effectiveness of the program. The program also has a network of personnel qualified to conduct naked-eye inspections of the cervix, who could easily be trained to perform triage colposcopy. The incorporation of new prevention strategies could reduce the deaths of Chilean women and correct inequities.