Effects of long-term HbA1c variability on serious infection risks in patients with type 2 diabetes and the influence of age, sex and ethnicity: A cohort study of primary care data.

AIMS: Long-term HbA1c (glycated haemoglobin) variability is associated with micro- and macrovascular complications in Type 2 diabetes (T2D). We explored prospective associations between HbA1c variability and serious infections, and how these vary by HbA1c level, age, sex and ethnicity. METHODS: 411,963 T2D patients in England, aged 18-90, alive on 01/01/2015 in the Clinical Practice Research Datalink with ≥ 4 HbA1c measurements during 2011-14. Poisson regression estimated incidence rate ratios (IRRs) for infections requiring hospitalisation during 2015-19 by HbA1c variability score (HVS) and average level, adjusting for confounders, and stratified by age, sex, ethnicity and average level. Attributable risk fractions (AF) were calculated using reference categories for variability (HVS < 20) and average level (42-48 mmol/mol). RESULTS: An increased infection risk (IRR > 1.2) was seen with even modest variability (HVS ≥ 20, 73 % of T2D patients), but only at higher average levels (≥64 mmol/mol, 27 % patients). Estimated AFs were markedly greater for variability than average level (17.1 % vs. 4.1 %). Associations with variability were greater among older patients, and those with lower HbA1c levels, but not observed among Black ethnicities. CONCLUSIONS: HbA1c variability between T2D patients' primary care visits appears to be associated with more serious infections than average level overall. Well-designed trials could test whether these associations are causal.

A matched cohort study evaluating the risks of infections in people with type 1 diabetes and their associations with glycated haemoglobin.

AIMS: People with type 1 diabetes (T1D) have raised infection rates compared to those without, but how these risks vary by age, sex and ethnicity, or by glycated haemoglobin (HbA1c), remain uncertain. METHODS: 33,829 patients with T1D in Clinical Practice Research Datalink on 01/01/2015 were age-sex-ethnicity matched to two non-diabetes patients. Infections were collated from primary care and linked hospitalisation records during 2015-2019, and incidence rate ratios (IRRs) were estimated versus non-diabetes. For 26,096 people with T1D, with ≥3 HbA1c measurements in 2012-2014, mean and coefficient of variation were estimated, and compared across percentiles. RESULTS: People with T1D had increased risk for infections presenting in primary care (IRR = 1.81, 95%CI 1.77-1.85) and hospitalisations (IRR = 3.37, 3.21-3.53) compared to non-diabetes, slightly attenuated after further adjustment. Younger ages and non-White ethnicities had greater relative risks, potentially explained by higher HbA1c mean and variability amongst people with T1D within these sub-groups. Both mean HbA1c and greater variability were strongly associated with infection risks, but the greatest associations were at the highest mean levels (hospitalisations IRR = 4.09, 3.64-4.59) for >97 versus ≤53 mmol/mol. CONCLUSIONS: Infections are a significant health burden in T1D. Improved glycaemic control may reduce infection risks, while prompter infection treatments may reduce hospital admissions.

What are the perceptions and concerns of people living with diabetes and National Health Service staff around the potential implementation of AI-assisted screening for diabetic eye disease? Development and validation of a survey for use in a secondary care screening setting.

INTRODUCTION: The English National Health Service (NHS) Diabetic Eye Screening Programme (DESP) performs around 2.3 million eye screening appointments annually, generating approximately 13 million retinal images that are graded by humans for the presence or severity of diabetic retinopathy. Previous research has shown that automated retinal image analysis systems, including artificial intelligence (AI), can identify images with no disease from those with diabetic retinopathy as safely and effectively as human graders, and could significantly reduce the workload for human graders. Some algorithms can also determine the level of severity of the retinopathy with similar performance to humans. There is a need to examine perceptions and concerns surrounding AI-assisted eye-screening among people living with diabetes and NHS staff, if AI was to be introduced into the DESP, to identify factors that may influence acceptance of this technology. METHODS AND ANALYSIS: People living with diabetes and staff from the North East London (NEL) NHS DESP were invited to participate in two respective focus groups to codesign two online surveys exploring their perceptions and concerns around the potential introduction of AI-assisted screening.Focus group participants were representative of the local population in terms of ages and ethnicity. Participants' feedback was taken into consideration to update surveys which were circulated for further feedback. Surveys will be piloted at the NEL DESP and followed by semistructured interviews to assess accessibility, usability and to validate the surveys.Validated surveys will be distributed by other NHS DESP sites, and also via patient groups on social media, relevant charities and the British Association of Retinal Screeners. Post-survey evaluative interviews will be undertaken among those who consent to participate in further research. ETHICS AND DISSEMINATION: Ethical approval has been obtained by the NHS Research Ethics Committee (IRAS ID: 316631). Survey results will be shared and discussed with focus groups to facilitate preparation of findings for publication and to inform codesign of outreach activities to address concerns and perceptions identified.

Infarcts of a Cardioembolic Source Mimicking Lacunar Infarcts: Case Series With Clinical and Radiological Correlation.

Lacunar strokes are the hallmark of cerebral small vessel disease. There are several well-established mechanisms for the pathogenesis of lacunar stroke, but the cardioembolic mechanism is not well-established. Three cases of acute ischemic stroke following elective cardiac and cerebral catheterization are reported. These cases had typical lacunar-looking infarcts on neuroimaging despite strong evidence of an embolic source with temporal correlation. Awareness of such findings and pathogenesis may help investigational workup and management of these patients.

Are the Pilots Onboard? Equipping Radiologists for Clinical Implementation of AI.

The incorporation of artificial intelligence into radiological clinical workflow is on the verge of being realized. To ensure that these tools are effective, measures must be taken to educate radiologists on tool performance and failure modes. Additionally, radiology systems should be designed to avoid automation bias and the potential decline in radiologist performance. Designed solutions should cater to every level of expertise so that patient care can be enhanced and risks reduced. Ultimately, the radiology community must provide education so that radiologists can learn about algorithms, their inputs and outputs, and potential ways they may fail. This manuscript will present suggestions on how to train radiologists to use these new digital systems, how to detect AI errors, and how to maintain underlying diagnostic competency when the algorithm fails.

Evaluating Ethnic Variations in the Risk of Infections in People With Prediabetes and Type 2 Diabetes: A Matched Cohort Study.

OBJECTIVE: People living with type 2 diabetes (T2D) are at higher infection risk, but it is unknown how this risk varies by ethnicity or whether the risk is similarly observed in people with nondiabetic hyperglycemia ("prediabetes"). RESEARCH DESIGN AND METHODS: We included 527,151 patients in England with T2D and 273,216 with prediabetes, aged 18-90, and alive on 1 January 2015 on the Clinical Practice Research Datalink. Each was matched to two patients without diabetes or prediabetes on age, sex, and ethnic group. Infections during 2015-2019 were collated from primary care and linked hospitalization records. Infection incidence rate ratios (IRRs) for those with prediabetes or T2D were estimated, unadjusted and adjusted for confounders. RESULTS: People with T2D had increased risk for infections presenting in primary care (IRR 1.51, 95% CI 1.51-1.52) and hospitalizations (IRR 1.91, 1.90-1.93). This was broadly consistent overall within each ethnic group, although younger White T2D patients (age <50) experienced a greater relative risk. Adjustment for socioeconomic deprivation, smoking, and comorbidity attenuated associations, but IRRs remained similar by ethnicity. For prediabetes, a significant but smaller risk was observed (primary care IRR 1.35, 95% CI 1.34-1.36; hospitalization IRR 1.33, 1.31-1.35). These were similar within each ethnicity for primary care infections, but less consistent for infection-related hospitalizations. CONCLUSIONS: The elevated infection risk for people with T2D appears similar for different ethnic groups and is also seen in people with prediabetes. Infections are a substantial cause of ill-health and health service use for people with prediabetes and T2D. This has public health implications with rising prediabetes and diabetes prevalence.

Prevalence of co-morbidity and history of recent infection in patients with neuromuscular disease: A cross-sectional analysis of United Kingdom primary care data.

BACKGROUND: People with neuromuscular disease (NMD) experience a broader range of chronic diseases and health symptoms compared to the general population. However, no comprehensive analysis has directly quantified this to our knowledge. METHODS: We used a large UK primary care database (Clinical Practice Research Datalink) to compare the prevalence of chronic diseases and other health conditions, including recent infections between 23,876 patients with NMD ever recorded by 2019 compared to 95,295 age-sex-practice matched patients without NMD. Modified Poisson regression estimated Prevalence Ratios (PR) to summarise the presence of the disease/condition ever (or for infections in 2018) in NMD patients versus non-NMD patients. RESULTS: Patients with NMD had significantly higher rates for 16 of the 18 conditions routinely recorded in the primary care Quality and Outcomes Framework (QOF). Approximately 1-in-10 adults with NMD had ≥4 conditions recorded (PR = 1.39, 95%CI 1.33-1.45). Disparities were more pronounced at younger ages (18-49). For other (non-QOF) health conditions, significantly higher recorded levels were observed for rarer events (pulmonary embolism PR = 1.96 95%CI 1.76-2.18, hip fractures PR = 1.65 95%CI 1.47-1.85) as well as for more common primary care conditions (constipation PR = 1.52 95%CI 1.46-1.57, incontinence PR = 1.52 95%CI 1.44-1.60). The greatest co-morbidity burden was in patients with a myotonic disorder. Approximately 1-in-6 (17.1%) NMD patients had an infection recorded in the preceding year, with the risk of being hospitalised with an infection nearly double (PR = 1.92, 95%CI 1.79-2.07) compared to non-NMD patients. CONCLUSION: The burden of chronic co-morbidity among patients with NMD is extremely high compared to the general population, and they are also more likely to present in primary and secondary care for acute events such as infections.

Genome Sequences of Two Gordonia rubripertincta Cluster DJ Bacteriophages, Pherobrine and Burley.

Pherobrine and Burley are siphoviruses infecting Gordonia rubripertincta. Pherobrine has a 60,305-bp genome with 89 predicted protein-coding genes, and Burley has a 60,111-bp genome with 90 predicted protein-coding genes. Both phages are assigned to cluster DJ, where they share 78% gene content similarity with each other.

Nonpharmacological Interventions to Lengthen Sleep Duration in Healthy Children: A Systematic Review and Meta-analysis.

Importance: Adequate sleep duration is necessary for many aspects of child health, development, and well-being, yet sleep durations for children are declining, and effective strategies to increase sleep in healthy children remain to be elucidated. Objective: To determine whether nonpharmaceutical interventions to improve sleep duration in healthy children are effective and to identify the key components of these interventions. Data Sources: CENTRAL, MEDLINE, Embase, PsycINFO, Web of Science Core collection, ClinicalTrials.gov, and WHO trials databases were searched from inception to November 15, 2021. Study Selection: Randomized clinical trials of interventions to improve sleep duration in healthy children were independently screened by 2 researchers. A total of 28 478 studies were identified. Data Extraction and Synthesis: Data were processed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) reporting guideline. Random-effects meta-analytic models were used to estimate pooled effect sizes. Main Outcomes and Measures: Difference in sleep duration, measured in minutes. Results: A total of 13 539 child participants from 45 randomized clinical trials were included. Of these, 6897 (50.9%) were in the intervention group and 6642 (49.1%) in the control group, and the mean age ranged from 18 months to 19 years. Pooled results indicate that sleep interventions were associated with 10.5 minutes (95% CI, 5.6-15.4) longer nocturnal sleep duration. There was substantial variation between trials. Sources of variation that were not associated with the study effect size included age group, whether the population was identified as having a sleep problem or being at a socioeconomic disadvantage (eg, coming from a low-income family or area), method of assessment of sleep duration (objective vs subjective), location of intervention delivery (home vs school), whether interventions were delivered in person or used parental involvement, whether behavioral theory was used, environmental change, or had greater or lower intensity. Interventions that included earlier bedtimes were associated with a 47-minute sleep extension (95% CI, 18.9-75.0; 3 trials) compared with remaining studies (7.4 minutes; 95% CI, 2.9-11.8; 42 trials) (P = .006 for group difference). Trials of shorter duration (6 months or less) had larger effects. Conclusions and Relevance: Interventions focused on earlier bedtimes may offer a simple, pragmatic, effective way to meaningfully increase sleep duration that could have important benefits for child health.

Undergraduate medical teaching with remote consultations in general practice: a realist evaluation.

BACKGROUND: Supervisors historically educated students in primary care in face-to-face contexts; as a result of COVID-19, students now experience patient consultations predominantly remotely. There is a paucity of evidence regarding the facilitators and barriers to supervising students for excellent educational impact in the remote consultation environment. AIM: To understand the facilitators and barriers to educating medical students using remote consultations in primary care, and the consequences for students in terms of educational impact. DESIGN & SETTING: A realist evaluation methodology was adopted to identify causal chains of contexts, mechanisms, and outcomes, describing how the teaching and learning functioned on a sample of medical students and GP tutors from two medical schools in London, UK. METHOD: An initial programme theory was developed from the literature and a scoping exercise informed the data collection tools. Qualitative data were collected through online questionnaires (49 students, 19 tutors) and/or a semi-structured interview (eight students, two tutors). The data were coded to generate context-mechanisms-outcome configurations outlining how the teaching and learning operated. RESULTS: The results demonstrated a sequential style of supervision can positively impact student engagement and confidence, and highlighted a need to address student preparation for remote patient examinations. Students found passive observation of remote patient encounters disengaging, and, in addition, reported isolation that impacted negatively on their experiences and perceptions of primary care. CONCLUSION: Student and tutor experiences may improve through considering the supervision style adopted by tutors, and through interventions to reduce student isolation and disengagement when using remote patient consultations in primary care.

Prevalence and incidence of neuromuscular conditions in the UK between 2000 and 2019: A retrospective study using primary care data.

BACKGROUND: In the UK, large-scale electronic primary care datasets can provide up-to-date, accurate epidemiological information on rarer diseases, where specialist diagnoses from hospital discharges and clinic letters are generally well recorded and electronically searchable. Current estimates of the number of people living with neuromuscular disease (NMD) have largely been based on secondary care data sources and lacked direct denominators. OBJECTIVE: To estimate trends in the recording of neuromuscular disease in UK primary care between 2000-2019. METHODS: The Clinical Practice Research Datalink (CPRD) database was searched electronically to estimate incidence and prevalence rates (per 100,000) for a range of NMDs in each year. To compare trends over time, rates were age standardised to the most recent CPRD population (2019). RESULTS: Approximately 13 million patients were actively registered in each year. By 2019, 28,230 active patients had ever received a NMD diagnosis (223.6), which was higher among males (239.0) than females (208.3). The most common classifications were Guillain-Barre syndrome (40.1), myasthenia gravis (33.7), muscular dystrophy (29.5), Charcot-Marie-Tooth (29.5) and inflammatory myopathies (25.0). Since 2000, overall prevalence grew by 63%, with the largest increases seen at older ages (≥65-years). However, overall incidence remained constant, though myasthenia gravis incidence has risen steadily since 2008, while new cases of muscular dystrophy fell over the same period. CONCLUSIONS: Lifetime recording of many NMDs on primary care records exceed current estimates of people living with these conditions; these are important data for health service and care planning. Temporal trends suggest this number is steadily increasing, and while this may partially be due to better recording, it cannot be simply explained by new cases, as incidence remained constant. The increase in prevalence among older ages suggests increases in life expectancy among those living with NMDs may have occurred.

Risk factors for excess all-cause mortality during the first wave of the COVID-19 pandemic in England: A retrospective cohort study of primary care data.

BACKGROUND: The COVID-19 pandemic's first wave in England during spring 2020 resulted in an approximate 50% increase in all-cause mortality. Previously, risk factors such as age and ethnicity, were identified by studying COVID-related deaths only, but these were under-recorded during this period. OBJECTIVE: To use a large electronic primary care database to estimate the impact of risk factors (RFs) on excess mortality in England during the first wave, compared with the impact on total mortality during 2015-19. METHODS: Medical history, ethnicity, area-based deprivation and vital status data were extracted for an average of 4.8 million patients aged 30-104 years, for each year between 18-March and 19-May over a 6-year period (2015-2020). We used Poisson regression to model total mortality adjusting for age and sex, with interactions between each RF and period (pandemic vs. 2015-19). Total mortality during the pandemic was partitioned into "usual" and "excess" components, assuming 2015-19 rates represented "usual" mortality. The association of each RF with the 2020 "excess" component was derived as the excess mortality ratio (EMR), and compared with the usual mortality ratio (UMR). RESULTS: RFs where excess mortality was greatest and notably higher than usual were age >80, non-white ethnicity (e.g., black vs. white EMR = 2.50, 95%CI 1.97-3.18; compared to UMR = 0.92, 95%CI 0.85-1.00), BMI>40, dementia, learning disability, severe mental illness, place of residence (London, care-home, most deprived). By contrast, EMRs were comparable to UMRs for sex. Although some co-morbidities such as cancer produced EMRs significantly below their UMRs, the EMRs were still >1. In contrast current smoking has an EMR below 1 (EMR = 0.80, 95%CI 0.65-0.98) compared to its UMR = 1.64. CONCLUSIONS: Studying risk factors for excess mortality during the pandemic highlighted differences from studying cause-specific mortality. Our approach illustrates a novel methodology for evaluating a pandemic's impact by individual risk factor without requiring cause-specific mortality data.

Vaccination uptake amongst older adults from minority ethnic backgrounds: A systematic review.

BACKGROUND: Older adults from minority ethnic backgrounds are at increased risk of contracting COVID-19 and developing severe infection and have increased risk of mortality. Whilst an age-based vaccination approach prioritising older groups is being implemented worldwide, vaccine hesitancy is high amongst minority ethnic groups. METHODS AND FINDINGS: We conducted a systematic review and convergent synthesis to systematically examine perceptions of vaccinations amongst older adults from minority ethnic backgrounds. We included studies that reported on perceptions, beliefs, and attitudes towards vaccinations in older adults aged ≥65 years from a minority ethnic background. We excluded studies of vaccinations in investigation or development, studies focused on specific medical conditions, studies where ethnic background or age group was unidentifiable, systematic reviews, editorials, and conference abstracts. We searched MEDLINE, Embase, Virtual Health Library, Web of Science, Cochrane Library, medRxiv, and PROSPERO databases from inception to 15 July 2021. Risk of bias for studies was assessed using the Mixed Methods Appraisal Tool. The quality of evidence of collective outcomes was estimated using the Grading of Recommendations Assessment, Development and Evaluation-Confidence in the Evidence from Reviews of Qualitative research (GRADE-CERQual) framework. A total of 28 eligible studies conducted between 1997 and 2020 were included in the final analysis (17 quantitative surveys, 8 focus group or interview studies, 2 mixed methods studies, and 1 case-control study). The majority were US studies in English or Spanish, except for 6 studies set in Hong Kong, 2 studies in Japan, 1 study in Brazil, and 1 multi-centre study (including China, Indonesia, Turkey, South Korea, Greece, UK, Brazil, and Nigeria). In total, 28,262 individuals with an estimated mean age of 69.8 years were included, 63.2% of whom were female. We summarised the common concepts and themes across studies and populations using a convergent synthesis analysis. Thirteen themes categorised as barriers or facilitators were identified and grouped into structural factors-healthcare provider and system related, patient related, and policy and operational-and were analysed by minority ethnic group. The main limitation of the study was the predominance of studies from the US and East Asia. CONCLUSIONS: In this systematic review, we found that factors influencing vaccination uptake involve healthcare provider and system, patient-related, and governance-level factors that are specific to the older ethnic minority community being served. The evidence included in this review is supported by high or moderate certainty and can be translated to practice and policy. A tailored, multi-level approach combining increased education, access, and culturally competent discussions with trusted healthcare professionals to address health beliefs can maximise the potential impact of widespread vaccination policies.

One-Lung Ventilation in a Patient With Necrotizing Pneumonia Complicated by a Bronchopleural Fistula.

A 32-year-old male with morbid obesity presented to the emergency department with a one-week history of shortness of breath and productive cough. This patient had previously been evaluated at an urgent care facility, diagnosed with pneumonia, and prescribed oral antibiotics. This patient's worsening shortness of breath and productive cough led this patient to seek further care at the emergency department. Chest radiography revealed acute respiratory distress syndrome (ARDS) with an empyema in the right pleural space. He was admitted to the intensive care unit and subsequently intubated due to severely compromised cardiopulmonary function. The patient then underwent irrigation of the chest cavity and chest tube placement for drainage of the right-sided empyema. Surgical cultures revealed growth of Streptococcus anginosus and appropriate antibiotics were started. The patient's pulmonary function continued to deteriorate and this patient was placed on venous to venous extracorporeal membrane oxygenation (VV ECMO). Due to continued respiratory failure and a persistent air leak, a double-lumen endotracheal tube (DLT) was exchanged to initiate one-lung ventilation (OLV) to optimize ventilation and protect the lung containing the empyema. Over the following days, worsening leukocytosis and atelectasis were noted upon imaging prompting cardiothoracic surgery to return to the operating room to perform a right posterolateral thoracotomy and full right lung decortication. The procedure was successful and a bronchopleural fistula (BPF) was observed, secondary to the necrotizing pneumonia. The observation of the fistula explained the persistent air leak and issues maintaining adequate oxygenation. OLV through a DLT was continued over the following days, and the patient's pulmonary status and leukocytosis ultimately began to improve over the next two weeks. This patient was then able to be weaned off the EMCO device and was extubated. The patient was stabilized and discharged to a rehabilitation facility for further recovery. This case highlights how the use of lung isolation techniques were essential in the recovery of this patient with an estimated 50% mortality rate due to significant pulmonary injury from necrotizing pneumonia and complicated by a BPF.

Tabes Dorsalis in a Patient Presenting With Right Lower Extremity Paresthesia and Cervical Spine Pain.

Syphilitic myelitis, also known as tabes dorsalis, is a disease affecting the posterior columns of the spinal cord and dorsal roots and presents as sensory ataxia and neuropathic pain and less commonly as paresthesia and gastrointestinal disturbance. Tabes dorsalis is the clinical manifestation of a previous infection with syphilis, and the average latency period from initial infection to presentation of symptoms is approximately 25 years. This is a rarely encountered manifestation of syphilis since the widespread usage of antibiotics. Penicillin G is the mainstay therapy of neurosyphilis and has been shown to improve and resolve spinal cord lesions associated with tertiary syphilis. We present a case of tabes dorsalis in a 56-year-old female with a history of extensive autoimmune disease who initially presented with neck pain and numbness of the right lower extremity. The unique nature of this case lies in the patient's clinical course, as her symptoms were initially attributed to her history of autoimmune disease. A reactive CSF-VDRL (cerebrospinal fluid Venereal Disease Research Laboratory) test and MRI findings led clinicians to suspect neurosyphilis and begin penicillin G. The patient began to show significant clinical improvement after penicillin G therapy was begun and was discharged to a rehabilitation facility to continue antibiotics and begin aggressive physical therapy.

Pediatric spinal cord infarction following a minor trauma: a case report.

INTRODUCTION: Pediatric spinal cord infarction is a rare entity that presents a diagnostic challenge at the emergency department. Ischemic spinal cord infarction can occur in the setting of trauma, cardiovascular malformation, or postoperatively. We report a case of anterior spinal artery infarction following seemingly minor trauma in an otherwise healthy 14-year-old male. CASE PRESENTATION: A 14-year-old male presented with unprovoked sudden-onset stabbing back pain earlier that day. The patient then demonstrated bilateral lower extremities weakness while at the emergency department. After extensive diagnostic workup, the patient was diagnosed with anterior spinal artery territory infarction involving the thoracic spinal cord. Minor trauma to the thoracic spinal cord was detected on imaging and was believed to be the culprit of this event. DISCUSSION: Given the rarity of spinal cord ischemia, a high index of suspicion and extensive workup of patients presenting with clinical weakness are needed for accurate diagnosis and to avoid the eventual poor outcome. With so few reports in the literature regarding spinal cord ischemia in the pediatric population, accurate diagnosis is often delayed until after irreversible events have already taken place. Our case report of anterior spinal artery distribution thoracic cord infarct following a minor trauma was diagnosed by axial thin-slice DWI MRI with an otherwise negative workup.

The effects of step-count monitoring interventions on physical activity: systematic review and meta-analysis of community-based randomised controlled trials in adults.

BACKGROUND: Step-count monitors (pedometers, body-worn trackers and smartphone applications) can increase walking, helping to tackle physical inactivity. We aimed to assess the effect of step-count monitors on physical activity (PA) in randomised controlled trials (RCTs) amongst community-dwelling adults; including longer-term effects, differences between step-count monitors, and between intervention components. METHODS: Systematic literature searches in seven databases identified RCTs in healthy adults, or those at risk of disease, published between January 2000-April 2020. Two reviewers independently selected studies, extracted data and assessed risk of bias. Outcome was mean differences (MD) with 95% confidence intervals (CI) in steps at follow-up between treatment and control groups. Our preferred outcome measure was from studies with follow-up steps adjusted for baseline steps (change studies); but we also included studies reporting follow-up differences only (end-point studies). Multivariate-meta-analysis used random-effect estimates at different time-points for change studies only. Meta-regression compared effects of different step-count monitors and intervention components amongst all studies at ≤4 months. RESULTS: Of 12,491 records identified, 70 RCTs (at generally low risk of bias) were included, with 57 trials (16,355 participants) included in meta-analyses: 32 provided change from baseline data; 25 provided end-point only. Multivariate meta-analysis of the 32 change studies demonstrated step-counts favoured intervention groups: MD of 1126 steps/day 95%CI [787, 1466] at ≤4 months, 1050 steps/day [602, 1498] at 6 months, 464 steps/day [301, 626] at 1 year, 121 steps/day [- 64, 306] at 2 years and 434 steps/day [191, 676] at 3-4 years. Meta-regression of the 57 trials at ≤4 months demonstrated in mutually-adjusted analyses that: end-point were similar to change studies (+ 257 steps/day [- 417, 931]); body-worn trackers/smartphone applications were less effective than pedometers (- 834 steps/day [- 1542, - 126]); and interventions providing additional counselling/incentives were not better than those without (- 812 steps/day [- 1503, - 122]). CONCLUSIONS: Step-count monitoring leads to short and long-term step-count increases, with no evidence that either body-worn trackers/smartphone applications, or additional counselling/incentives offer further benefit over simpler pedometer-based interventions. Simple step-count monitoring interventions should be prioritised to address the public health physical inactivity challenge. SYSTEMATIC REVIEW REGISTRATION: PROSPERO number CRD42017075810 .