Krebs von den Lungen 6 (KL-6) as a marker for disease severity and persistent radiological abnormalities following COVID-19 infection at 12 weeks

Introduction Acute presentations of COVID-19 infection vary, ranging from asymptomatic carriage through to severe clinical manifestations including acute respiratory distress syndrome (ARDS). Longer term sequelae of COVID-19 infection includes lung fibrosis in a proportion of patients. Krebs von den Lungen 6 (KL-6) is a mucin like glycoprotein that has been proposed as a marker of pulmonary epithelial cell injury. We sought to determine whether KL-6 was a marker of 1) the severity of acute COVID-19 infection, or 2) the persistence of symptoms/radiological abnormalities at medium term follow up. Methods Prospective single centre observational study. Results Convalescent KL-6 levels were available for 93 patients (male 63%, mean age 55.8 years) who attended an 12-week follow up appointment after being admitted to hospital with COVID-19. For 67 patients a baseline KL-6 result was available for comparison. There was no significant correlations between baseline KL-6 and the admission CXR severity score or clinical severity NEWS score. Furthermore, there was no significant difference in the baseline KL-6 level and an initial requirement for oxygen on admission or the severity of acute infection as measured at 28 days. There was no significant difference in the 12-week KL-6 level and the presence or absence of subjective breathlessness but patients with abnormal CT scans at 12 weeks had significantly higher convalescent KL-6 levels compared to the remainder of the cohort (median 1101 IU/ml vs 409 IU/ml). Conclusions The association between high KL-6 levels at 12 weeks and persisting CT abnormalities (GGO/fibrosis), is a finding that requires further exploration. Whether KL-6 may help differentiate those patients with persisting dyspnoea due to complications rather than deconditioning or dysfunctional breathing alone, is an important future research question.

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Severe COVID-19 is associated with sustained biochemical disturbances and prolonged symptomatology; A retrospective single-centre cohort study

10.1101/2021.09.02.21262599 ◽

2021 ◽

Author(s):

Marija Simjanoska ◽

Zan Mitrev ◽

Gianluca Villa ◽

Daniel O. Griffin ◽

Rodney A. Rosalia

Keyword(s):

Clinical Presentation ◽

Acute Infection ◽

Laboratory Data ◽

Clinical Manifestations ◽

Clinical Severity ◽

Single Centre ◽

Post Discharge ◽

Patients Experience ◽

Biochemical Abnormalities

AbstractIntroductionCoronavirus disease 2019 (COVID-19) is associated with significant acute clinical manifestations, and reports indicate that some patients experience prolonged symptomatology and morbidity. These late clinical manifestations have been termed Post-Acute Sequelae of COVID-19 (PASC) and hypothesised to be associated with clinical severity in the acute infection phase and biochemical abnormalities.AimEvaluate the incidence of PASC in previously hospitalised COVID-19 patients and compare the admission and follow-up levels of biochemical parameters stratified according to baseline clinical severity.MethodsN = 168 COVID-19 patients previously hospitalised at the Zan Mitrev Clinic in Skopje, North Macedonia, with matched laboratory data at baseline and follow-up clinical visit > 30 days post-discharge, were stratified according to National Institute of Health clinical severity guidelines as mild, moderate, severe or critical according to admission clinical presentation. We assessed the incidence of PASC and compared the biochemical profile.ResultsThe median hospitalisation and clinical follow-up period were 11 (9-20) and 53 (30-105) days. The overall incidence of PASC was 56.5% (95/168); most PASC cases were confined to the severe sub-group (61/101, 61.4%). Contrary to mild and moderate cases and a healthy “non-COVID-19” control cohort, we observed that severe COVID-19 cases experienced sustained biochemical disturbances, most notably elevated D-dimers and Ferritin of 600 ng/ml (283-1168) and 432 ng/ml (170-916), respectively.ConclusionsPreviously hospitalised severe COVID-19 patients are more likely to experience Post-Acute Sequelae of COVID-19 and prolonged biochemical disturbances, evident by abnormal values of D-dimers and Ferritin.

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Azithromycin in patients with Covid-19; a systematic review and metanalysis

10.1101/2021.08.03.21261414 ◽

2021 ◽

Author(s):

Luis Ayerbe ◽

Ivo Forgnone ◽

Carlos Risco-Risco ◽

Maria Perez-Pinar ◽

Salma Ayis

Keyword(s):

Systematic Review ◽

Clinical Severity ◽

Future Research ◽

Controlled Trials ◽

Clinical Settings ◽

Cochrane Central Register ◽

Random Effects Models ◽

Central Register ◽

Significant Difference ◽

Observational Design

Background: Azithromycin (AZM) has been widely used in the management of Covid-19. However, the evidence on its actual effects remains disperse and difficult to apply in clinical settings. This systematic review and metanalysis summarizes the studies on the beneficial and adverse effect of AZM in patients with Covid-19. Methods: The PRISMA 2020 statement criteria were followed. Randomized controlled trials (RCTs) and observational studies comparing clinical outcomes of patients treated, and not treated, with AZM, indexed until the 5th of July 2021, were searched in PubMed, Embase, The Web of Science, Scopus, The Cochrane Central Register of Controlled Trials, and MedRXivs. We used Random-effects models to estimate pooled effect size from aggregate data. Results: The initial search produced 4950 results. Finally, 16 studies, five RCTs and 11 with an observational design, with a total of 22984 patients, were included. The metanalysis showed no difference in mortality for those treated, or not, with AZM, OR: 0.95 (0.79-1.13). There was also no significant difference for those treated, and not, with AZM in need for hospital admission or time to admission from ambulatory settings, clinical severity, need for intensive care, or adverse effects. Conclusions: These results presented in this review do not support the use of AZM in the management of Covid-19. They also show that any harm caused to the patient who received it is unlikely. Future research on treatment for patients with Covid-19 may need to focus on other drugs

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What evidence is there that parenting interventions reduce child abuse and neglect among maltreating families? A systematic review

Developmental Child Welfare ◽

10.1177/2516103219893383 ◽

2019 ◽

Vol 1 (4) ◽

pp. 374-393

Author(s):

Sarah Whitcombe-Dobbs ◽

Michael Tarren-Sweeney

Keyword(s):

Child Abuse ◽

Child Maltreatment ◽

Selection Criteria ◽

Research Question ◽

Child Abuse And Neglect ◽

Intervention Group ◽

Future Research ◽

Parenting Interventions ◽

Significant Difference ◽

Abuse And Neglect

In families where child abuse and neglect have already occurred, there is a strong imperative to provide interventions that reduce or eliminate harm done to children. Parenting programs lack tailoring for the needs of maltreating parents, and maltreating parents themselves are a heterogeneous group with varying needs. The literature on the effectiveness of parenting interventions for high-risk parents is limited, and this scarcity of knowledge can result in child protection cases being treated as a natural experiment. For children who experience ongoing maltreatment by their parents, the most stringent test for effectiveness goes beyond an improvement in positive parenting skills—child abuse and neglect must reduce or be eliminated. The present review addressed the research question What evidence is there that parenting interventions conducted with parents who maltreat their children, reduce the incidence of further child maltreatment? Databases were searched for trials of parenting interventions where participants were maltreating parents and outcome data included an objective measure of child abuse and neglect. Nine studies satisfied the selection criteria and are summarized. Four studies reported a statistically significant difference between groups in favor of the intervention group for two parenting interventions, Parent–Child Interaction Therapy and SafeCare. However, the review concludes that none of the reviewed parenting interventions have been demonstrated to be effective at reducing all types of child maltreatment through a high-quality RCT. Previous research is compromised by several critical methodological limitations, including low participant recruitment and retention, and narrow selection criteria. Recommendations are offered for future research on parenting interventions that aim to reduce child abuse and neglect.

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A Longitudinal SARS-CoV-2 Biorepository for COVID-19 Survivors with and without Post-Acute Sequelae

10.21203/rs.3.rs-493160/v1 ◽

2021 ◽

Author(s):

Stephanie M LaVergne ◽

Stromberg Sophia ◽

Bridget A Baxter ◽

Tracy L Webb ◽

Taru S Dutt ◽

...

Keyword(s):

Demographic Data ◽

Acute Infection ◽

Exercise Intolerance ◽

Future Research ◽

Clinical Trial Registration ◽

Targeted Interventions ◽

Persistent Symptoms ◽

Northern Colorado ◽

History Of

Abstract BackgroundSARS-CoV-2 has swept across the globe, causing millions of deaths worldwide. Though most survive, many experience symptoms of COVID-19 for months after acute infection. Successful prevention and treatment of acute COVID-19 infection and its associated sequelae is dependent on in-depth knowledge of viral pathology across the spectrum of patient phenotypes and physiologic responses. Longitudinal biobanking provides a valuable resource of clinically integrated, easily accessed, and quality-controlled samples for researchers to study differential multi-organ system responses to SARS-CoV-2 infection, post-acute sequelae of COVID-19 (PASC), and vaccination. MethodsAdults with a history of a positive SARS-CoV-2 nasopharyngeal PCR are actively recruited from the community or hospital settings to enroll in the Northern Colorado SARS-CoV-2 Biorepository (NoCo-COBIO). Blood, saliva, stool, nasopharyngeal specimens, and extensive clinical and demographic data are collected at 4 time points over 6 months. Patients are assessed for PASC during longitudinal follow-up by physician led symptom questionnaires and physical exams. This clinical trial registration is NCT05603677.ResultsWe have enrolled and collected samples from 119 adults since July 2020, with 66% follow-up rate. Forty-nine percent of participants assessed with a symptom surveillance questionnaire (N=37 of 75) had PASC at any time during follow-up (up to 8 months post infection). Ninety-three percent of hospitalized participants developed PASC, while 23% of those not requiring hospitalization developed PASC. At 90-174 days post SARS-CoV-2 diagnosis, 67% of all participants had persistent symptoms (N=37 of 55), and 85% percent of participants who required hospitalization during initial infection (N=20) still had symptoms. The most common symptoms reported after 15 days of infection were fatigue, loss of smell, loss of taste, exercise intolerance, and cognitive dysfunction. ConclusionsPatients who were hospitalized for COVID-19 were significantly more likely to have PASC than those not requiring hospitalization, however 23% of patients who were not hospitalized also developed PASC. This patient-matched, multi-matrix, longitudinal biorepository from COVID-19 survivors with and without PASC will allow for current and future research to better understand the pathophysiology of disease and to identify targeted interventions to reduce risk for PASC. Registered 27 October 2020 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04603677.

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Clinical Analysis of Chronic Active EBV Infection with Coronary Artery Dilatation and Matched Case-control Study

10.21203/rs.3.rs-98303/v1 ◽

2020 ◽

Author(s):

Ang Wei ◽

Honghao Ma ◽

Liping Zhang ◽

Zhigang Li ◽

Yitong Guan ◽

...

Keyword(s):

Coronary Artery ◽

Serum Ferritin ◽

Clinical Manifestations ◽

Control Group ◽

Hematopoietic Stem ◽

Ebv Infection ◽

Coronary Artery Dilatation ◽

Tnf Α ◽

Significant Difference

Abstract Objective To investigate the clinical characteristics, treatment, prognosis, and risk factors of chronic active EBV infection (CAEBV) associated with coronary artery dilatation (CAD) in children.Methods Children with CAEBV associated with CAD hospitalized in Beijing Children’s Hospital, Capital Medical University, from March 2016 to December 2019 were analyzed. At the same time, children with CAEBV without CAD were selected as the control group, matched by sex, age, treatment and admission time. The clinical manifestations, laboratory and ultrasonic examinations, treatment and prognosis of the children were collected in both groups.Results There were 10 children with CAEBV combined with CAD, accounting for 8.9% (10/112) of CAEBV patients at the same period, which including 6 males and 4 females, with onset age of 6.05 (2.8-14.3) years. The median follow-up time was 20 (6-48) months. All the patients had high copies of EBV-DNA in whole blood 1.18x107（1.90x105-3.96x107）copies/mL and plasma 1.81x104（1.54x103-1.76x106）copies/mL, and the Epstein-Barr virus encoded small RNA in biopsy was all positive. Among the 10 children, 8 had bilateral CAD, with 2 patients unilateral. After diagnosis, 7 children were treated with L-DEP chemotherapy in our hospital. After chemotherapy, four patients accepted allo-genetic Hematopoietic Stem Cell Transplantation (HSCT). The others were waiting for HSCT. By the end of the follow-up, CAD had returned to normal in 3 patients, and the time from diagnosis of CAD to recovery was 21 (18-68) d. The level of LDH, serum ferritin, TNF-α and IL-10 had statistically significant difference between the two groups (P=0.009, 0.008, 0.026 and 0.030). There were no significant differences in survival rate between the two groups (P=0.416).Conclusion The incidence of CAEBV with CAD was low. CAEBV with CAD did not influence the prognosis. Patients with CAEBV had high LDH, serum ferritin, TNF-α and IL-10 in the early onset were prone to have CAD.

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Quantification of venous reflux parameters using duplex scanning and air plethysmography

Phlebology The Journal of Venous Disease ◽

10.1258/026835507779700635 ◽

2007 ◽

Vol 22 (1) ◽

pp. 20-28 ◽

Cited By ~ 16

Author(s):

T Yamaki ◽

M Nozaki ◽

H Sakurai ◽

M Takeuchi ◽

T Kono ◽

...

Keyword(s):

Venous Insufficiency ◽

Femoral Vein ◽

Clinical Manifestations ◽

Clinical Severity ◽

Venous Reflux ◽

Discrimination Power ◽

Group I ◽

Significant Difference ◽

Air Plethysmography ◽

Group Ii

Objective: To compare different duplex-and air plethysmography (APG)-derived parameters between patients with relatively early and those with advanced chronic venous insufficiency (CVI), and to investigate the indicative parameters reflecting the progression of CVI. Methods: Design: Prospective study at the University Hospital. Patients: In total 686 limbs in 574 patients at various clinical stages of CVI were included. The clinical manifestations were categorized according to the CEAP (clinical, aetiologic, anatomic and pathophysiologic) classification, and the patients were divided into two groups: group I (C1-3EP,SAS,D,PPR,O, relatively early stage of CVI) and group II (C4-6EP,SAS,D,PPR,O, advanced CVI). The distribution of venous insufficiency including the sapheno-femoral junction (SFJ), great saphenous vein (GSV), sapheno–popliteal junction (SPJ), common femoral vein (CFV), femoral vein (FV), popliteal vein (POPV), thigh perforators (TPV) and calf perforators (CPV) was determined by duplex ultrasound. The main duplex-derived parameters assessed were the reflux time (RT; s), peak reflux velocity (PRV; cm/s) and peak reflux flow (PRF; mL/s). The venous reflux was assumed to be present if the duration of reflux was ≥0.5 s. The data obtained by APG were on VV (mL), VFI (mL/s), EF (%) and RVF (%). Results: There was no significant difference in overall superficial venous reflux between the groups ( P=0.331). The frequency of deep and perforating vein incompetence differed only when superficial reflux was included in group II. The VFI and RVF were significantly higher in secondary CVI than in primary CVI ( P=0.0001, 0.003, respectively). In the secondary CVI, patients with reflux and obstruction showed significantly higher RVF than those with reflux alone ( P=0.003). The RT did not improve the discrimination power between the groups. In contrast, the PRV had significant discrimination power at the SFJ ( P<0.0001) and SPJ ( P=0.022), and in the GSV ( P<0.0001), the FV ( P=0.017), and the POPV ( P=0.0003). The PRF was significantly higher in group II at the SFJ ( P<0.0001), in the GSV ( P=0.002), in the CFV ( P=0.011), in the FV ( P=0.027), and the POPV ( P=0.016). Conclusions: This present study has suggested the importance of superficial venous insufficiency in the development of advanced CVI. In the secondary CVI, obstruction affects the RVF alone. The PRV and PRF are better parameters than the RT for discrimination of clinical severity in both superficial and deep venous insufficiency, and should be used to quantify venous valvular insufficiency.

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Evaluation of factors influencing tick bites and tick-borne infections: a longitudinal study

Parasites & Vectors ◽

10.1186/s13071-021-04751-0 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Bo Bødker Jensen ◽

Mie Topholm Bruun ◽

Per Moestrup Jensen ◽

Andreas Kristian Pedersen ◽

Pierre-Edouard Fournier ◽

...

Keyword(s):

Blood Donors ◽

Seroconversion Rate ◽

Clinical Manifestations ◽

Weather Conditions ◽

Igg Antibodies ◽

Tick Bites ◽

Significant Difference ◽

Study Population ◽

June July

Abstract Background Various tick-borne infections like borreliosis and rickettsiosis pose a health risk to humans in many parts of the world. We investigated seroprevalence of and seroconversion to Borrelia burgdorferi and Rickettsia spp. and relation to tick-bites, weather and clinical manifestations in Denmark. Methods Blood donors were enrolled at the Hospital of Southern Jutland in June–July with follow-up November–February of 2018 and 2019. Blood samples were collected, and a questionnaire regarding tick bites, potential exposures and symptoms was completed at each visit. Samples were tested for presence of IgM and IgG antibodies directed against B. burgdorferi and Rickettsia spp. using R. helvetica and R. felis as antigens. Data were examined for correlation between tick bites, serological results, potential exposures and symptoms. Results Two-hundred and fourteen (93 follow-ups) and 130 (38 follow-ups) blood donors were included in 2018 and 2019, respectively. The total borrelia seroconversion rate was 6.3% (CI 2.1–10.5), while the prevalence of IgM and IgG antibodies was 7.8% (CI 4.9–10.6) and 6.7% (CI 4–9.3), respectively. Seroconversion to Rickettsia spp. was detected in one participant. Tick bites and seroconversion were not significantly associated with the reported unspecific symptoms, but unspecific symptoms were common in the study population. There was no significant difference in number of tick bites or seroconversion/prevalence between seasons with highly alternating weather. Conclusions Results suggest that weather conditions in an individual year have a limited impact. Anti-Borrelia-antibodies do not seem to persist in serum for several years. Rickettsiosis is of limited concern in Denmark. Graphic abstract

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A110 PATIENT-GUIDED COMPLICATION TRACKING SYSTEM (PACTS): BUILDING ALLIANCES WITH PATIENTS FOR THE CONTINUED IMPROVEMENT OF POST-PROCEDURAL OUTCOMES.

Journal of the Canadian Association of Gastroenterology ◽

10.1093/jcag/gwab002.108 ◽

2021 ◽

Vol 4 (Supplement_1) ◽

pp. 87-89

Author(s):

L Calman T’ien ◽

C A Macdonnell ◽

J Yonge ◽

C Galorport ◽

R A Enns

Keyword(s):

Response Rate ◽

Tracking System ◽

Response Rates ◽

Future Research ◽

Median Response ◽

Design Elements ◽

Design Changes ◽

Significant Difference ◽

Message Service

Abstract Background In Healthcare, interventions using Short Message Service (SMS) are growing as more patients have mobile phones. To date, studies have investigated using SMS to remind patients of upcoming appointments and provide preventative medical care. Although SMS interventions exist, little is known about their potential as a post-procedural follow-up tool. SMS follow-up systems present a unique opportunity for clinics to provide support to patients having unplanned post-procedural events. Moreover, the identification of these cases promotes the adoption of preventative measures. Before SMS follow-up programs can be integrated in clinics, proof-of-concept research needs to be conducted to assess the feasibility of this intervention. Aims This study aims to determine intervention design elements to maximize the response rate of a novel follow-up program implemented at St. Paul’s Hospital in Vancouver, BC. Methods An iterative prospective study was conducted to assess the effects of various design features on the response rate of an SMS follow-up system. Outpatients having a colonoscopy and/or gastroscopy at St. Paul’s Hospital between 11/19-03/20 were considered for inclusion in this pilot. Patients were asked to participate if they understood Grade 10-level English and had a mobile phone. For this pilot, a PAtient-guided Complication Tracking System (PACTS) was designed to send SMS to patients one week post-procedure. During each program round, adjustments were made to PACTS with the goal of increasing the response rate. The design changes made to the pilot were cumulative. One-way ANOVA and Tukey’s Honestly Significant Difference tests were completed to assess response rate differences between rounds. Results A total of 1829 patients met the inclusion criteria and consented to participate in the pilot. The overall median response rate was 93%. ANOVA test revealed a statistically significant difference in response rates between rounds, F(6, 196) = 3.369, p = 0.0035. Only the mean response rates between Rounds 1 and 7 yielded a significant pairwise difference (p < 0.001). Conclusions The PACTS pilot demonstrates that high response rates are achievable by SMS follow-up systems. This study identified several design elements to optimize SMS intervention response rates. These features included: sending a 1st SMS that explains the program’s purpose, sending a 2nd SMS to participants that did not respond to the first, and providing pilot information to patients upon admission and discharge. Future research on SMS follow-up systems should explore designing a program that can be integrated in clinics with minimal staff involvement. Funding Agencies None

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A longitudinal SARS-CoV-2 biorepository for COVID-19 survivors with and without post-acute sequelae

BMC Infectious Diseases ◽

10.1186/s12879-021-06359-2 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Stephanie M. LaVergne ◽

Sophia Stromberg ◽

Bridget A. Baxter ◽

Tracy L. Webb ◽

Taru S. Dutt ◽

...

Keyword(s):

Demographic Data ◽

Acute Infection ◽

Exercise Intolerance ◽

Future Research ◽

Clinical Trial Registration ◽

Targeted Interventions ◽

Persistent Symptoms ◽

Link Type ◽

History Of

Abstract Background SARS-CoV-2 has swept across the globe, causing millions of deaths worldwide. Though most survive, many experience symptoms of COVID-19 for months after acute infection. Successful prevention and treatment of acute COVID-19 infection and its associated sequelae is dependent on in-depth knowledge of viral pathology across the spectrum of patient phenotypes and physiologic responses. Longitudinal biobanking provides a valuable resource of clinically integrated, easily accessed, and quality-controlled samples for researchers to study differential multi-organ system responses to SARS-CoV-2 infection, post-acute sequelae of COVID-19 (PASC), and vaccination. Methods Adults with a history of a positive SARS-CoV-2 nasopharyngeal PCR are actively recruited from the community or hospital settings to enroll in the Northern Colorado SARS-CoV-2 Biorepository (NoCo-COBIO). Blood, saliva, stool, nasopharyngeal specimens, and extensive clinical and demographic data are collected at 4 time points over 6 months. Patients are assessed for PASC during longitudinal follow-up by physician led symptom questionnaires and physical exams. This clinical trial registration is NCT04603677. Results We have enrolled and collected samples from 119 adults since July 2020, with 66% follow-up rate. Forty-nine percent of participants assessed with a symptom surveillance questionnaire (N = 37 of 75) had PASC at any time during follow-up (up to 8 months post infection). Ninety-three percent of hospitalized participants developed PASC, while 23% of those not requiring hospitalization developed PASC. At 90–174 days post SARS-CoV-2 diagnosis, 67% of all participants had persistent symptoms (N = 37 of 55), and 85% percent of participants who required hospitalization during initial infection (N = 20) still had symptoms. The most common symptoms reported after 15 days of infection were fatigue, loss of smell, loss of taste, exercise intolerance, and cognitive dysfunction. Conclusions Patients who were hospitalized for COVID-19 were significantly more likely to have PASC than those not requiring hospitalization, however 23% of patients who were not hospitalized also developed PASC. This patient-matched, multi-matrix, longitudinal biorepository from COVID-19 survivors with and without PASC will allow for current and future research to better understand the pathophysiology of disease and to identify targeted interventions to reduce risk for PASC. Registered 27 October 2020 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04603677.

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Evaluation of the Effectiveness of Digital Technology Interventions to Reduce Loneliness in Older Adults: Systematic Review and Meta-analysis (Preprint)

10.2196/preprints.24712 ◽

2020 ◽

Author(s):

Syed Ghulam Sarwar Shah ◽

David Nogueras ◽

Hugo Cornelis van Woerden ◽

Vasiliki Kiparoglou

Keyword(s):

Older Adults ◽

Clinical Trials ◽

Digital Technology ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Public Health Issue ◽

Future Research ◽

Physical And Mental Health ◽

Significant Difference

BACKGROUND Loneliness is a serious public health issue, and its burden is increasing in many countries. Loneliness affects social, physical, and mental health, and it is associated with multimorbidity and premature mortality. In addition to social interventions, a range of digital technology interventions (DTIs) are being used to tackle loneliness. However, there is limited evidence on the effectiveness of DTIs in reducing loneliness, especially in adults. The effectiveness of DTIs in reducing loneliness needs to be systematically assessed. OBJECTIVE The objective of this study is to assess the effectiveness of DTIs in reducing loneliness in older adults. METHODS We conducted electronic searches in PubMed, MEDLINE, CINAHL, Embase, and Web of Science for empirical studies published in English from January 1, 2010, to July 31, 2019. The study selection criteria included interventional studies that used any type of DTIs to reduce loneliness in adults (aged ≥18 years) with a minimum intervention duration of 3 months and follow-up measurements at least 3 months after the intervention. Two researchers independently screened articles and extracted data using the PICO (participant, intervention, comparator, and outcome) framework. The primary outcome measure was loneliness. Loneliness scores in both the intervention and control groups at baseline and at follow-up at 3, 4, 6, and 12 months after the intervention were extracted. Data were analyzed via narrative synthesis and meta-analysis using RevMan (The Cochrane Collaboration) software. RESULTS A total of 6 studies were selected from 4939 screened articles. These studies included 1 before and after study and 5 clinical trials (4 randomized clinical trials and 1 quasi-experimental study). All of these studies enrolled a total of 646 participants (men: n=154, 23.8%; women: n=427, 66.1%; no gender information: n=65, 10.1%) with an average age of 73-78 years (SD 6-11). Five clinical trials were included in the meta-analysis, and by using the random effects model, standardized mean differences (SMDs) were calculated for each trial and pooled across studies at the 3-, 4-, and 6-month follow-ups. The overall effect estimates showed no statistically significant difference in the effectiveness of DTIs compared with that of usual care or non-DTIs at follow-up at 3 months (SMD 0.02; 95% CI −0.36 to 0.40; P=.92), 4 months (SMD −1.11; 95% CI −2.60 to 0.38; P=.14), and 6 months (SMD −0.11; 95% CI −0.54 to 0.32; P=.61). The quality of evidence was very low to moderate in these trials. CONCLUSIONS Our meta-analysis shows no evidence supporting the effectiveness of DTIs in reducing loneliness in older adults. Future research may consider randomized controlled trials with larger sample sizes and longer durations for both the interventions and follow-ups. INTERNATIONAL REGISTERED REPORT RR2-10.1136/bmjopen-2019-032455

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