Risk of transmission of HIV to infants during breast/chest feeding when mothers/birthing parents living with HIV are on antiretroviral therapy: a protocol for a rapid review.

INTRODUCTION: HIV is a major public health issue affecting millions globally. Women and girls account for 46% of new HIV infections in 2022 and approximately 1.3 million females become pregnant every year. Vertical transmission of HIV from persons living with HIV (PLHIV) to infants may occur through different modalities, such as through breast/chest feeding. Notably, 82% of PLHIV who chose to breast/chest feed are on antiretroviral therapy (ART) when feeding their infants. Precise estimates of the risk of postpartum transmission to infants during breast/chest feeding at varying viral load levels remain a significant gap in the literature. METHODS AND ANALYSIS: A rapid systematic search of electronic databases will be conducted from January 2005 to the present, including Medline, Embase and Global Health. The objective of this rapid review is to explore and assess the available evidence on the effect of varying viral load levels on the risk of HIV transmission to infants during breast/chest feeding when the birthing or gestational parent living with HIV is on ART. Study characteristics will be summarised and reported to support the narrative summary of the findings. The focus will be on the absolute risk of HIV transmission from birthing parent to infant during chest/breast feeding. The findings will also be stratified by month, including the risk of HIV transmission for 6 months and greater than 6 months postpartum. We will ascertain the risk of bias using A Measurement Tool to Assess Systematic Reviews 2, Quality of Prognosis Studies and Downs and Black checklist for the appropriate study type. A summary score will not be calculated, rather the strengths and limitations of the studies will be narratively described. ETHICS AND DISSEMINATION: No human subjects will be involved in the research. The findings of this rapid review will inform a future systematic review and will be disseminated through peer-reviewed publications, presentations and conferences. PROSPERO REGISTRATION NUMBER: CRD42024499393.

Neuroanatomical location of brain metastases from solid tumours based on pathology: An analysis of 511 patients with a comparison to the provided clinical history.

Brain metastases are a frequent occurrence in neuropathology practices. The literature on their neuroanatomical location is frequently derived from radiological analyses. This work examines brain metastases through the lens of pathology specimens. All brain surgical pathology reports for cases accessioned 2011-2020 were retrieved from a laboratory. Specimens were classified by neuroanatomical location, diagnosis and diagnostic category with a hierarchical free text string-matching algorithm (HFTSMA) and also subsequently audited. All reports classified as probable metastasis were reviewed by a pathologist. The provided history was compared to the final categorization by a pathologist. The cohort had 4,625 cases. The HFTSMA identified 854 cases (including metastases from a definite primary, metastases from primary not known and improperly classified cases). 514/854 cases had one definite primary site per algorithm and on report review 538/854 cases were confirmed as such. The 538 cases originated from 511 patients. Primaries from breast, gynecologic tract, and gastrointestinal tract not otherwise specified were most frequently found in the cerebellum. Kidney metastases were most frequently found in the occipital lobe. Lung, metastatic melanoma and colorectal primaries were most commonly found in the frontal lobe. The provided clinical history predicted the primary in 206 cases (40.3%), was discordant in 17 cases (3.3%) and non-contributory in 280 cases (54.8%). The observed distribution of the metastatic tumours in the brain is dependent on the primary site. In the majority (54.8%) of cases, the provided clinical history was non-contributory; this suggests surgeon-pathologist communication may have the potential for optimization.

Prevalence of Thyroid Transcription Factor-1 (TTF-1)-Negative Small Cell Carcinoma and Napsin A Positivity in Small Cell Carcinoma in a Cross-Sectional Study of Lung Core Biopsies.

Background The prevalence of thyroid transcription factor-1 (TTF-1) and napsin A expression are poorly characterized in lung core biopsies of small cell carcinoma. Locally, the TTF-1 clone is 8G7G3/1 (Agilent/Dako), and the napsin A clone is IP64 (Leica Biosystems). Methods All in-house lung core biopsy reports for cases accessioned at a regional laboratory from January 2011 to December 2020 were retrieved and analyzed using a validated hierarchical free-text string matching algorithm (HFTSMA) to establish the diagnosis. TTF-1 and napsin A were manually coded with the assistance of a logical text parsing tool. All TTF-1-negative small cell lung carcinoma (SCLC) cases had a full report review by pathologists. Results The cohort had 5,867 lung core biopsies, and 232 cases were confirmed as small cell carcinoma on pathologist review. TTF-1 immunostain results were available in 173 SCLC cases, and 16 cases of TTF-1-negative SCLC were confirmed on full report review. These 16 cases had at least one positive neuroendocrine (NE) marker and positive keratin staining; cases with mixed histology or positive CK5/6 staining were excluded. Ki-67 was done in 10/16 cases; the average Ki-67 was 75%. Napsin A was negative in 50/51 small cell carcinomas, and 0/3 TTF-1-negative SCLC had napsin A positivity. Conclusions Standardized immunostain reporting would simplify such analyses. Based on the cohort, approximately 9% (16/173) of SCLC is TTF-1 negative. Napsin A positivity in suspected small cell carcinoma should prompt consideration of an alternate diagnosis or explanation.

Risk of sexual transmission of HIV in the context of viral load suppression.

Background: In 2018, the Public Health Agency of Canada (PHAC) published a systematic review to calculate the risk of sexual transmission of human immunodeficiency virus (HIV) in the context of antiretroviral therapy (ART). In 2022, PHAC commissioned the Canadian Agency for Drugs and Technologies in Health (CADTH) to conduct a rapid review of evidence published since 2017. We undertook a meta-analysis of relevant studies from these two reviews. Methods: Studies from the rapid review that adequately assessed exposure (HIV viral load) and outcome (HIV seroconversion) were included and assessed for risk of bias (RoB) and certainty of evidence. Results were pooled to estimate the risk of HIV transmission per 100 person-years. Results: Three studies from the rapid review were eligible for inclusion and one was excluded after RoB assessment. In the remaining studies examining risk among people living with HIV who take ART and maintain a suppressed viral load (fewer than 200 copies/mL, measured every 4-6 months), no sexual transmissions of HIV were observed. The pooled incidence estimate based on these studies, and one from the 2018 PHAC review, was zero transmissions/100 person-years (95% CI: 0.00-0.10). No studies in the rapid review provided data on the risk of sexual transmission of HIV in situations of varying levels of viral load. Conclusion: This update highlights the consistency of evidence since the 2018 PHAC review. There remains no evidence of HIV transmission to sexual partners when a person living with HIV is on ART and maintains a suppressed viral load.

Opioid prescribing practices in trauma patients at discharge: An exploratory retrospective chart analysis.

This study examined the opioid prescribing patterns at discharge in the trauma center of a major Canadian hospital and compared them to the guidelines provided by the Illinois surgical quality improvement collaborative (ISQIC), a framework that has been recognized as being associated with reduced risk. This was a retrospective chart review of patient data from the trauma registry between January 1, 2018, and October 31, 2019. A total of 268 discharge charts of naïve opioid patients were included in the analysis. A Morphine Milligram Equivalents per day (MME/day) was computed for each patient who was prescribed opioids and compared with standard practice guidelines. About 75% of patients were prescribed opioids. More males (75%) than females (25%) were prescribed opioids to patients below 65 years old (91%). Best practice guidelines were followed in most cases. Only 16.6% of patients were prescribed over 50 mg MME/day, the majority (80.9%) were prescribed opioids for =<3 days and only 1% for >7 days. Only 7.5% were prescribed extended-release opioids and none were strong like fentanyl. Patients received a multimodal approach with alternatives to opioids in 88.9% of cases and 82.9% had a plan for opioid discontinuation. However, only 23.6% received an acute pain service referral. The majority of the prescriptions provided adhered to the best practice guidelines outlined by the ISQIC framework. These results are encouraging with respect to the feasibility of implementing opioid prescription guidelines effectively. However, routine monitoring is necessary to ensure that adherence is maintained.

Impact of the COVID-19 pandemic on non-small-cell lung cancer pathologic stage and presentation.

BACKGROUND: It is believed that the cessation of normative cancer care services during the COVID-19 pandemic may be resulting in pathologic upstaging and higher long-term mortality rates. We aimed to understand how the pandemic has affected our patients diagnosed with non-small-cell lung cancer (NSCLC). METHODS: We conducted a single-centre retrospective analysis to assess how the COVID-19 pandemic has affected patient referrals, pathologic stage of NSCLC, mortality rates and surgical procedures at our cancer care centre in Ontario, Canada. At our centre, physicians advocated for and followed recommendations that operations in cancer patients should be among the last procedures to be delayed. Patients were included if they were aged 18 years or older, were not receiving palliative care, and had been screened, diagnosed and treated for NSCLC (primary tumours). We compared outcomes between a prepandemic period (January 2019 to February 2020) and a period during the pandemic (March 2020 to February 2021). RESULTS: A total of 695 patients were included for statistical analysis, of whom 650 underwent surgery. There was no statistically significant difference in any of the outcomes of interest between patients seen before (n = 330) and during (n = 320) the pandemic. CONCLUSION: Cancer care services at our centre were maintained during the COVID-19 pandemic, and potential adverse effects on prognosis and survival that have been seen in other countries were avoided. The results inform health care providers how the effects of future pandemics can be blunted by using proactive preservative strategies and surgeon advocacy.

The histologic effects of neoadjuvant stereotactic body radiation therapy (SBRT) followed by pulmonary metastasectomy-rationale and protocol design for the Post SBRT Pulmonary Metastasectomy (PSPM) trial.

Background: For the local management of pulmonary malignancies, surgical resection and stereotactic body radiation therapy (SBRT) are mutually exclusive treatments. This study aims to assess the effectiveness of SBRT on reducing tumor viability at a histologic level in the context of pulmonary metastases. Methods: This protocol describes an open-label unblinded single-arm prospective Phase 2 trial to determine the effects of dual treatment of pulmonary metastasis amenable to curative resection using neoadjuvant SBRT followed by surgical resection, the Post SBRT Pulmonary Metastasectomy (PSPM) trial. Sample size require 39 patients, with an anticipated study duration of 30-36 months. Following completion of SBRT, eligible patients will be assessed at the 4-6-week mark by the treating radiation oncologist and thoracic surgeon with a post-treatment computed tomography (CT) of the chest. Patients with no disease progression will undergo scheduled surgical resection of all metastatic tumors at 8-12 weeks post SBRT. Patients will then be evaluated postoperatively at 30 days, and every 6 months for a total of 36 months with surveillance CT scans. Patients will also undergo sequential serologic evaluation of circulating tumor DNA (ctDNA) levels throughout their respective treatment pathway. The primary outcome of this study is the rate of complete pathologic response (pCR) following SBRT, assess using the International Association for the Study of Lung Cancer (IASLC) multidisciplinary recommendations for pathologic assessment of lung cancer resection specimens after neoadjuvant therapy. Secondary outcomes include overall survival (OS), disease free survival (DFS), local recurrence rates, cancer histology effects on pCR and treatment related complications, and treatment effect on ctDNA levels. Primary and secondary outcomes will be analyzed using Fisher's Exact test and Student's t-test based on data type. Cox-proportional hazard ratios will be used to evaluate OS and DFS, using the log rank test. Discussion: In evaluating the effect of SBRT on pulmonary metastasis at a histologic level, this trial may increase the use of this modality in selected patients who would otherwise only undergo surgery for disease that has already metastasized. Also, the trial provides secondary benefits of evaluating the abscopal effects of radiation on pulmonary metastatic disease, and serves as a platform for more comprehensive large-scale research in this field. Trial Registration: ClinicalTrials.gov identifier: NCT04160143 (HiREB: 7925).

Survival effects of time to surgery for Stage I lung cancer: A population-based study.

OBJECTIVES: To examine the impact of time to surgery (TTS) on survival among patients with stage I non-small cell lung cancer (NSCLC). METHODS: All patients in the Canadian province of Ontario with stage I NSCLC from 2007 to 2017 were included. A logistic regression identified the predictors of TTS and a flexible parametric model estimated survival rates based on TTS. RESULTS: Over the study period, 6428 patients with stage I NSCLC undergoing surgical resection were identified, of which 62.5% had TTS >28 days. Less than half these patients (40.8%) underwent open resection, with 19.3% undergoing open sublobar and 21.5% undergoing open lobectomy. Adenocarcinoma and squamous cell carcinoma tumors accounted for 33.3% and 22.0% of cases, respectively. The majority (85.6%) of patients lived in urban areas within 50 km of a regional cancer center (76.9%). Variables that predicted TTS >28 days include age and extent of resection. After adjustment for VATS vs. open resection, age, sex, frailty, year of diagnosis, histology of tumor, and extent of resection, the hazard ratio for TTS >28 days was 1.26 (95%CI:1.13-1.40), indicating a 26% increased risk of all-cause mortality (p < 0.0001). The highest 5-year survival was observed for patients with stage I disease undergoing resection within 28 days. CONCLUSIONS: The present study found age and extent of resection to be associated with increased TTS. Importantly, patients with TTS >28 days had reduced long-term survival.

Smartphone Alcohol Use Disorder Recovery Apps: Cross-sectional Survey of Behavioral Intention to Use.

BACKGROUND: Alcohol use disorder (AUD) carries a huge health and economic cost to society. Effective interventions exist but numerous challenges limit their adoption, especially in a pandemic context. AUD recovery apps (AUDRA) have emerged as a potential complement to in-person interventions. They are easy to access and show promising results in terms of efficacy. However, they rely on individual adoption decisions and remain underused. OBJECTIVE: The aim of this survey study is to explore the beliefs that determine the intention to use AUDRA. METHODS: We conducted a cross-sectional survey study of people with AUD. We used the Unified Theory of Acceptance and Use of Technology, which predicts use and behavioral intention to use based on performance expectancy, effort expectancy, social influence, and facilitating conditions. Participants were recruited directly from 2 sources; first, respondents at addiction treatment facilities in Ontario, Canada, were contacted in person, and they filled a paper form; second, members from AUD recovery support groups on social media were contacted and invited to fill an internet-based survey. The survey was conducted between October 2019 and June 2020. RESULTS: The final sample comprised 159 participants (124 involved in the web-based survey and 35 in the paper-based survey) self-identifying somewhat or very much with AUD. Most participants (n=136, 85.5%) were aware of AUDRA and those participants scored higher on performance expectancy, effort expectancy, and social influence. Overall, the model explains 35.4% of the variance in the behavioral intention to use AUDRA and 11.1% of the variance in use. Social influence (P=.31), especially for women (P=.23), and effort expectancy (P=.25) were key antecedents of behavioral intention. Facilitating conditions were not significant overall but were moderated by age (P=.23), suggesting that it matters for older participants. Performance expectancy did not predict behavioral intention, which is unlike many other technologies but confirms other findings associated with mobile health (mHealth). Open-ended questions suggest that privacy concerns may significantly influence the use of AUDRA. CONCLUSIONS: This study suggests that unlike many other technologies, the adoption of AUDRA is not mainly determined by utilitarian factors such as performance expectancy. Rather, effort expectancy and social influence play a key role in determining the intention to use AUDRA.

The Effect of Major and Minor Complications After Lung Surgery on Length of Stay and Readmission.

The effect of post-operative adverse events (AEs) on patient outcomes such as length of stay (LOS) and readmissions to hospital is not completely understood. This study examined the severity of AEs from a high-volume thoracic surgery center and its effect on the patient postoperative LOS and readmissions to hospital. This study includes patients who underwent an elective lung resection between September 2018 and January 2020. The AEs were grouped as no AEs, 1 or more minor AEs, and 1 or more major AEs. The effects of the AEs on patient LOS and readmissions were examined using a survival analysis and logistic regression, respectively, while adjusting for the other demographic or clinical variables. Among 488 patients who underwent lung surgery, (Wedge resection [n = 100], Segmentectomy [n = 51], Lobectomy [n = 310], Bilobectomy [n = 10], or Pneumonectomy [n = 17]) for either primary (n = 440) or secondary (n = 48) lung cancers, 179 (36.7%) patients had no AEs, 264 (54.1%) patients had 1 or more minor AEs, and 45 (9.2%) patients had 1 or more major AEs. Overall, the median of LOS was 3 days which varied significantly between AE groups; 2, 4, and 8 days among the no, minor, and major AE groups, respectively. In addition, type of surgery, renal disease (urinary tract infection [UTI], urinary retention, or acute kidney injury), and ASA (American Society of Anesthesiology) score were significant predictors of LOS. Finally, 58 (11.9%) patients were readmitted. Readmission was significantly associated with AE group (P = 0.016). No other variable could significantly predict patient readmission. Overall, postoperative AEs significantly affect the postoperative LOS and readmission rates.

A risk model to predict an unplanned admission to the intensive care unit following lung resection.

OBJECTIVES: The goal of this study was to develop a risk-adjusting model to stratify the risk of an unplanned admission to the intensive care unit (following lung resection). METHODS: We performed a retrospective analysis of 3123 patients undergoing anatomical lung resections (2014-2019) in 2 centres. A risk score was developed by testing several variables for a possible association with a subsequent ICU admission using stepwise logistic regression analyses, validated by the bootstrap resampling technique. Variables associated with ICU admission were assigned weighted scores based on their regression coefficients. These scores were summed for each patient to generate the ICU risk score, and patients were grouped into risk classes. RESULTS: A total of 103 patients (3.3%) required an unplanned admission to the ICU after the operation. The average ICU stay was 17.6 days. The following variables remained significantly associated with ICU admission following logistic regression: male gender (P = 0.004), body mass index <18.5 (P = 0.002), predicted postoperative forced expiratory volume in 1 s < 60% (P = 0.004), predicted postoperative carbon monoxide lung diffusion capacity <50% (P = 0.013), open access (P = 0.004) and pneumonectomy (P = 0.041). All variables were weighted 1 point except body mass index <18.5 (2 points). The final ICU risk score ranged from 0 to 7 points. Patients were grouped into 6 risk classes showing an incremental unplanned ICU admission rate: class A (score 0), 0.7%; class B (score 1), 1.7%; class C (score 2), 3%; class D (score 3), 7.1%; class E (score 4), 12%; and class F (score > 4), 13% (P < 0.001). CONCLUSIONS: This risk score may assist in reliably planning the response to a sudden increase in the demand of critical care resources.

Contemporary trends in the level of evidence in general thoracic surgery clinical research.

OBJECTIVES: The large volume of scientific publications and the increasing emphasis on high-quality evidence for clinical decision-making present daily challenges to all clinicians, including thoracic surgeons. The objective of this study was to evaluate the contemporary trend in the level of evidence (LOE) for thoracic surgery clinical research. METHODS: All clinical research articles published between January 2010 and December 2017 in 3 major general thoracic surgery journals were reviewed. Five authors independently reviewed the abstracts of each publication and assigned a LOE to each of them using the 2011 Oxford Centre for Evidence-Based Medicine classification scheme. Data extracted from eligible abstracts included study type, study size, country of primary author and type of study designs. Three auditing processes were conducted to establish working definitions and the process was validated with a research methodologist and 2 senior thoracic surgeons. Intra-class correlation coefficient was calculated to assess inter-rater agreement. Chi-square test and Spearman correlation analysis were then used to compare the LOE between journals and by year of publication. RESULTS: Of 2028 publications reviewed and scored, 29 (1.4%) were graded level I, 75 (3.7%) were graded level II, 471 (23.2%) were graded level III, 1420 (70.2%) were graded level IV and 33 (1.6%) were graded level V (lowest level). Most publications (94.9%) were of lower-level evidence (III-V). There was an overall increasing trend in the lower LOE (P < 0.001). Inter-rater reliability was substantial with 95.5% (95%, confidence interval: 0.95-0.96) level of agreement between reviewers. CONCLUSIONS: General thoracic surgery literature consists mostly of lower LOE studies. The number of lower levels of evidence is dominating the recent publications, potentially indicating a need to increase the commitment to produce and disseminate higher-level evidence in general thoracic surgery.

Cost-effectiveness of diagnostic strategies for venous thromboembolism: a systematic review.

Guideline developers consider cost-effectiveness evidence in decision making to determine value for money. This consideration in the guideline development process can be informed either by formal and dedicated economic evaluations or by systematic reviews of existing studies. To inform the American Society of Hematology guideline on the diagnosis of venous thromboembolism (VTE), we conducted a systematic review focused on the cost-effectiveness of diagnostic strategies for VTE within the guideline scope. We systematically searched Medline (Ovid), Embase (Ovid), National Health Service Economic Evaluation Database, and the Cost-effectiveness Analysis Registry; summarized; and critically appraised the economic evidence on diagnostic strategies for VTE. We identified 49 studies that met our inclusion criteria, with 26 on pulmonary embolism (PE) and 24 on deep vein thrombosis (DVT). For the diagnosis of PE, strategies including d-dimer to exclude PE were cost-effective compared with strategies without d-dimer testing. The cost-effectiveness of computed tomography pulmonary angiogram (CTPA) in relation to ventilation-perfusion (V/Q) scan was inconclusive. CTPA or V/Q scan following ultrasound or d-dimer results could be cost-effective or even cost saving. For DVT, studies supporting strategies with d-dimer and/or ultrasound were cost-effective, supporting the recommendation that for patients at low (unlikely) VTE risk, using d-dimer as the initial test reduces the need for diagnostic imaging. Our systematic review informed the American Society of Hematology guideline recommendations about d-dimer, V/Q scan and CTPA for PE diagnosis, and d-dimer and ultrasound for DVT diagnosis.

Pneumonectomy for lung cancer in the elderly: lessons learned from a multicenter study.

BACKGROUND: 60% of patients diagnosed with lung cancer are older than 65 years and are at risk for substandard treatment due to a reluctance to recommend surgery. Pneumonectomy remains a high risk procedure especially in elderly patients. Nevertheless, the impact of age and neoadjuvant treatment on outcomes after pneumonectomy is still not well described. METHODS: We performed a multicentric retrospective study, analyzing outcomes of patients older than 70 years who underwent pneumonectomy for central primary lung malignancy between January 2009 and June 2019 in 7 thoracic surgery departments: Lucerne and Bern (Switzerland), Hamilton (Canada), Alicante (Spain), Monza (Italy), London (UK), Leuven (Belgium). Survival was estimated with Kaplan-Meier, and differences in survival were determined by log-rank analysis. We investigated pre- and post-operative prognostic factors using Cox proportional hazards regression model; multivariable analysis was performed only with variables, which were statistically significant at the invariable analysis. RESULTS: A total of 136 patients were included in the study. Mean age was 73.8 years (SD 3.6). 24 patients (17.6%) had an induction treatment (chemotherapy alone in 15 patients and chemo-radiation in 9). Mean length of stay (LOS) was 12.6 days (SD 10.39) and 74 patients (54.4%) had experienced a post-operative complication: 29 (21.3%) had a pulmonary complication, 33 (24.3%) had a cardiac complication and in 12 cases (8.8%) patients experienced both cardiac and pulmonary complications. 16 patients were readmitted [median LOS 13.7 days (range, 2-39 days)] and of those 14 (10.3%) required redo surgery. Median overall survival (OS) of the entire cohort was 38 months (95% CI: 29.9-46.1 months); in-hospital mortality was 1.5%, 30-day mortality rate was 3.7%, while 90-day mortality was 8.8% accounting for 5 and 12 patients respectively. Patients receiving neo-adjuvant therapy did not experience a higher incidence of postoperative complications (P=0.633), did not have a longer postoperative course (P=0.588), nor did they have an increased mortality rate (P=0.863). CONCLUSIONS: Age should not be considered an absolute contraindication for pneumonectomy in elderly patients even after neoadjuvant treatment. It has become apparent that especially in these patients, a patient-tailored approach with a careful selection should be used to define the risk-benefit balance.

Systematic review and meta-analysis of outcomes in patients with suspected pulmonary embolism.

Prompt evaluation and therapeutic intervention of suspected pulmonary embolism (PE) are of paramount importance for improvement in outcomes. We systematically reviewed outcomes in patients with suspected PE, including mortality, incidence of recurrent PE, major bleeding, intracranial hemorrhage, and postthrombotic sequelae. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase for eligible studies, reference lists of relevant reviews, registered trials, and relevant conference proceedings. We included 22 studies with 15 865 patients. Among patients who were diagnosed with PE and discharged with anticoagulation, 3-month follow-up revealed that all-cause mortality was 5.69% (91/1599; 95% confidence interval [CI], 4.56-6.83), mortality from PE was 1.19% (19/1597; 95% CI, 0.66-1.72), recurrent venous thromboembolism (VTE) occurred in 1.38% (22/1597; 95% CI: 0.81-1.95), and major bleeding occurred in 0.90% (2/221%; 95% CI, 0-2.15). In patients with a low pretest probability (PTP) and negative D-dimer, 3-month follow-up revealed mortality from PE was 0% (0/808) and incidence of VTE was 0.37% (4/1094; 95% CI: 0.007-0.72). In patients with intermediate PTP and negative D-dimer, 3-month follow-up revealed that mortality from PE was 0% (0/2747) and incidence of VTE was 0.46% (14/3015; 95% CI: 0.22-0.71). In patients with high PTP and negative computed tomography (CT) scan, 3-month follow-up revealed mortality from PE was 0% (0/651) and incidence of VTE was 0.84% (11/1302; 95% CI: 0.35-1.34). We further summarize outcomes evaluated by various diagnostic tests and diagnostic pathways (ie, D-dimer followed by CT scan).

Volunteer Impact on Health-Related Outcomes for Seniors: a Systematic Review And Meta-Analysis.

BACKGROUND: Volunteers are increasingly promoted to improve health-related outcomes for community-dwelling elderly without synthesized evidence for effectiveness. This systematic review and meta-analysis evaluates the effects of unpaid volunteer interventions on health-related outcomes for such seniors. METHODS: MEDLINE, EMBASE and Cochrane (CENTRAL) were searched up to November 2018. We included English language, randomized trials. Two reviewers independently identified studies, extracted data, and assessed evidence certainty (using GRADE). Meta-analysis used random-effects models. Univariate meta-regressions investigated the relationship between volunteer intervention effects and trial participant age, percentage females, and risk of bias. RESULTS: 28 included studies focussed on seniors with a variety of chronic conditions (e.g., dementia, diabetes) and health states (e.g., frail, palliative). Volunteers provided a range of roles (e.g., counsellors, educators and coaches). Low certainty evidence found that volunteers may improve both physical function (MD = 3.2 points on the 100-point SF-36 physical component score [PCS]; 95% CI: 1.09, 5.27) and physical activity levels (SMD = 0.5, 95% CI: 0.14 to 0.83). Adverse events were not increased. CONCLUSION: Volunteers may increase physical activity levels and subjective ratings of physical function for seniors without apparent harm. These findings support the WHO call to action on evidence-based policies to align health systems in support of older adults.

Management of heparin-induced thrombocytopenia: systematic reviews and meta-analyses.

Heparin-induced thrombocytopenia (HIT) is a prothrombotic adverse drug reaction occurring in <0.1% to 7% of patients receiving heparin products depending on the patient population and type of heparin. Management of HIT is highly dependent on a sequence of tests for which clinicians may or may not have the results when care decisions need to be made. We conducted systematic reviews of the effects of management strategies in persons with acute HIT, subacute HIT A or B, and remote HIT. We searched Medline, EMBASE, and the Cochrane Database through July 2019 for previously published systematic reviews and primary studies. Two investigators independently screened and extracted data and assessed the certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. We found primarily noncomparative studies and case series assessing effects of treatments, which led to low to very low certainty evidence. There may be little to no difference in the effects between nonheparin parenteral anticoagulants and direct oral anticoagulants in acute HIT. The benefits of therapeutic-intensity may be greater than prophylactic-intensity anticoagulation. Using inferior vena cava filters or platelet transfusion may result in greater harm than not using these approaches. Evidence for management in special situations, such as for patients undergoing cardiovascular interventions or renal replacement therapy, was also low to very low certainty. Additional research to evaluate nonheparin anticoagulants is urgently needed, and the development of novel treatments that reduce thrombosis without increasing hemorrhage should be a priority.

Systematic review and meta-analysis of test accuracy for the diagnosis of suspected pulmonary embolism.

Pulmonary embolism (PE) is a common, potentially life-threatening yet treatable condition. Prompt diagnosis and expeditious therapeutic intervention is of paramount importance for optimal patient management. Our objective was to systematically review the accuracy of D-dimer assay, compression ultrasonography (CUS), computed tomography pulmonary angiography (CTPA), and ventilation-perfusion (V/Q) scanning for the diagnosis of suspected first and recurrent PE. We searched Cochrane Central, MEDLINE, and EMBASE for eligible studies, reference lists of relevant reviews, registered trials, and relevant conference proceedings. 2 investigators screened and abstracted data. Risk of bias was assessed using Quality Assessment of Diagnostic Accuracy Studies-2 and certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework. We pooled estimates of sensitivity and specificity. The review included 61 studies. The pooled estimates for D-dimer sensitivity and specificity were 0.97 (95% confidence interval [CI], 0.96-0.98) and 0.41 (95% CI, 0.36-0.46) respectively, whereas CTPA sensitivity and specificity were 0.94 (95% CI, 0.89-0.97) and 0.98 (95% CI, 0.97-0.99), respectively, and CUS sensitivity and specificity were 0.49 (95% CI, 0.31-0.66) and 0.96 (95% CI, 0.95-0.98), respectively. Three variations of pooled estimates for sensitivity and specificity of V/Q scan were carried out, based on interpretation of test results. D-dimer had the highest sensitivity when compared with imaging. CTPA and V/Q scans (high probability scan as a positive and low/non-diagnostic/normal scan as negative) both had the highest specificity. This systematic review was registered on PROSPERO as CRD42018084669.

Diagnosis of deep vein thrombosis of the upper extremity: a systematic review and meta-analysis of test accuracy.

Upper extremity deep vein thrombosis (UEDVT) accounts for ≤10% of DVT and can be associated with morbidity and mortality. Accurate diagnosis and treatment are necessary for safe and effective patient management. We systematically reviewed the accuracy of D-dimer and duplex ultrasonography (US) for the evaluation of suspected first-episode UEDVT. We searched the Cochrane Central Register, OVID MEDLINE, EMBASE, and PubMed for eligible studies, reference lists of relevant reviews, registered trials, and relevant conference proceedings. We included prospective cross-sectional and cohort studies that evaluated test accuracy. Two investigators independently screened and collected data. The risk of bias was assessed using Quality Assessment of Diagnostic Accuracy Studies 2 and certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework. We pooled estimates of sensitivity and specificity. The review included 9 studies. The pooled estimates for D-dimer sensitivity and specificity were 0.96 (95% confidence interval [CI], 0.87-0.99) and 0.47 (95% CI, 0.43-0.52), respectively. The pooled estimates for duplex US sensitivity and specificity were 0.87 (95% CI, 0.73-0.94) and 0.85 (95% CI, 0.72-0.93), respectively. Certainty of evidence was moderate. In this review, we summarized the test accuracy (sensitivity and specificity) of D-dimer and duplex US for this indication. The sensitivity and specificity of the tests found in the present review should be considered in the context of whether they are used alone or in combination, which is dependent on the prevalence of disease in the population, the clinical setting in which the patient is being evaluated, cost, potential harms, and patient outcomes. This study was registered at PROSPERO as Systematic Review Registration Number CRD42018098488.

Pharmacologic thromboprophylaxis in adult patients undergoing neurosurgical interventions for preventing venous thromboembolism.

The impact of pharmacologic prophylaxis for venous thromboembolism in patients undergoing neurosurgical intervention remains uncertain. We reviewed the efficacy and safety of pharmacologic compared with nonpharmacologic thromboprophylaxis in neurosurgical patients. Three databases were searched through April 2018, including those for randomized controlled trials (RCTs) and for nonrandomized controlled studies (NRSs). Independent reviewers assessed the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Seven RCTs and 3 NRSs proved eligible. No studies reported on symptomatic proximal and distal deep vein thrombosis (DVT). Two RCTs reported on screening-detected proximal and distal DVTs. We used the findings of these 2 RCTs as the closest surrogate outcomes to inform the proximal and distal DVT outcomes. These 2 RCTs suggest that pharmacologic thromboprophylaxis may decrease the risk of developing asymptomatic proximal DVT (relative risk [RR], 0.50; 95% confidence interval [CI], 0.30-0.84; low certainty). Findings were uncertain for mortality (RR, 1.27; 95% CI, 0.57-2.86; low certainty), symptomatic pulmonary embolism (PE) (RR, 0.84; 95% CI, 0.03-27.42; very low certainty), asymptomatic distal DVT (RR, 0.54; 95% CI, 0.27-1.08; very low certainty), and reoperation (RR, 0.43; 95% CI, 0.06-2.84; very low certainty) outcomes. NRSs also reported uncertain findings for whether pharmacologic prophylaxis affects mortality (RR, 0.72; 95% CI, 0.46-1.13; low certainty) and PE (RR, 0.18; 95% CI, 0.01-3.76). For risk of bleeding, findings were uncertain in both RCTs (RR, 1.57; 95% CI, 0.70-3.50; low certainty) and NRSs (RR, 1.45; 95% CI, 0.30-7.12; very low certainty). In patients undergoing neurosurgical procedures, low certainty of evidence suggests that pharmacologic thromboprophylaxis confers benefit for preventing asymptomatic (screening-detected) proximal DVT with very low certainty regarding its impact on patient-important outcomes.