Pharmaceutical company representatives likely influence the prescribing habits and professional behaviors of physicians. The objective of this study was to systematically review the association ...between physicians' interactions with pharmaceutical companies and their clinical practices.
We used the standard systematic review methodology. Observational and experimental study designs examining any type of targeted interaction between practicing physicians and pharmaceutical companies were eligible. The search strategy included a search of MEDLINE and EMBASE databases up to July 2016. Two reviewers selected studies, abstracted data, and assessed risk of bias in duplicate and independently. We assessed the quality of evidence using the GRADE approach.
Twenty articles reporting on 19 studies met our inclusion criteria. All of these studies were conducted in high-income countries and examined different types of interactions, including detailing, industry-funded continuing medical education, and receiving free gifts. While all included studies assessed prescribing behaviors, four studies also assessed financial outcomes, one assessed physicians' knowledge, and one assessed their beliefs. None of the studies assessed clinical outcomes. Out of the 19 studies, 15 found a consistent association between interactions promoting a medication, and inappropriately increased prescribing rates, lower prescribing quality, and/or increased prescribing costs. The remaining four studies found both associations and lack of significant associations for the different types of exposures and drugs examined in the studies. A meta-analysis of six of these studies found a statistically significant association between exposure and physicians' prescribing behaviors (OR = 2.52; 95% CI 1.82-3.50). The quality of evidence was downgraded to moderate for risk of bias and inconsistency. Sensitivity analysis excluding studies at high risk of bias did not substantially change these results. A subgroup analysis did not find a difference by type of exposure.
There is moderate quality evidence that physicians' interactions with pharmaceutical companies are associated with their prescribing patterns and quality.
Venous thromboembolism (VTE) is a common complication among patients with cancer. Patients with cancer and VTE are at a markedly increased risk for morbidity and mortality.
These evidence-based ...guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in their decisions about the prevention and treatment of VTE in patients with cancer.
ASH formed a multidisciplinary guideline panel balanced to minimize potential bias from conflicts of interest. The guideline development process was supported by updated or new systematic evidence reviews. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess evidence and make recommendations.
Recommendations address mechanical and pharmacological prophylaxis in hospitalized medical patients with cancer, those undergoing a surgical procedure, and ambulatory patients receiving cancer chemotherapy. The recommendations also address the use of anticoagulation for the initial, short-term, and long-term treatment of VTE in patients with cancer.
Strong recommendations include not using thromboprophylaxis in ambulatory patients receiving cancer chemotherapy at low risk of VTE and to use low-molecular-weight heparin (LMWH) for initial treatment of VTE in patients with cancer. Conditional recommendations include using thromboprophylaxis in hospitalized medical patients with cancer, LMWH or fondaparinux for surgical patients with cancer, LMWH or direct oral anticoagulants (DOAC) in ambulatory patients with cancer receiving systemic therapy at high risk of VTE and LMWH or DOAC for initial treatment of VTE, DOAC for the short-term treatment of VTE, and LMWH or DOAC for the long-term treatment of VTE in patients with cancer.
Abstract
Context
Consumption of sugar-sweetened beverages (SSBs) among children has been associated with adverse health outcomes. Numerous behavioral interventions aimed at reducing the intake of ...SSBs among children have been reported, yet evidence of their effectiveness is lacking.
Objective
This systematic review explored the effectiveness of educational and behavioral interventions to reduce SSB intake and to influence health outcomes among children aged 4 to 16 years.
Data Sources
Seven databases were searched for randomized controlled trials published prior to September 2016. Studies identified were screened for eligibility.
Study Selection
Trials were included in the review if they met the PICOS (Population, Intervention, Comparison, Outcome, and Study design) criteria for inclusion of studies.
Data Extraction
Data were extracted by 2 reviewers following Cochrane guidelines and using Review Manager software.
Results
Of the 16 trials included, 12 were school based and 4 were community or home based. Only 3 trials provided data that could be pooled into a meta-analysis for evaluating change in SSB intake. Subgroup analyses showed a trend toward a significant reduction in SSB intake in participants in school-based interventions compared with control groups. Change in body mass index z scores was not statistically significant between groups.
Conclusions
The quality of evidence from included trials was considered moderate, and the effectiveness of educational and behavioral interventions in reducing SSB intake was modest.
Systematic Review Registration
PROSPERO registration number CRD42014004432.
Cancer increases the risk of thromboembolic events in patients including those receiving anticoagulation treatments.
To compare the efficacy and safety of low molecular weight heparin (LMWH) and oral ...anticoagulants for the long-term treatment of venous thromboembolism (VTE) in patients with cancer.
We conducted a comprehensive search for studies of anticoagulation in cancer patients including 1. a February 2013 electronic search of: the Cochrane Central Register of Controlled Trials (CENTRAL Issue 12, 2012), MEDLINE, and EMBASE; 2. a handsearch of conference proceedings; 3. checking of references of included studies; 4. use of the 'related citation' feature in PubMed; and 5. a search of clinicaltrials.gov for ongoing studies.
We included randomized controlled trials (RCTs) comparing long-term treatment with LMWH versus oral anticoagulants (vitamin K antagonist (VKA) or ximelagatran) in patients with cancer and symptomatic objectively confirmed VTE.
Using a standardized data form, we extracted data on methodological quality, participants, interventions and outcomes of interest: survival, recurrent VTE, major bleeding, minor bleeding, thrombocytopenia, and postphlebitic syndrome. We assessed the quality of evidence at the outcome level following the GRADE approach.
Of 9559 identified citations, 10 RCTs (11 reports) were eligible and reported data for 1981 patients with cancer. We excluded 14 studies in which patients with cancer constituted study subgroups, but did not report outcome data for them. Meta-analysis of seven RCTs comparing LMWH with VKA found no statistically significant survival benefit (hazard ratio (HR) 0.96; 95% confidence interval (CI) 0.81 to 1.14) but a statistically significant reduction in VTE (HR 0.47; 95% CI 0.32 to 0.71). The remaining findings did not exclude a beneficial or harmful effect of LMWH compared with VKA for the outcomes of major bleeding (RR 1.07; 95% CI 0.52 to 2.19), minor bleeding (RR 0.89; 95% CI 0.51 to 1.55), or thrombocytopenia (RR 0.98; 95% CI 0.57 to 1.66). We judged the quality of evidence as low for mortality, major bleeding, and minor bleeding, and as moderate for recurrent VTE.One RCT comparing dabigatran with VKA did not exclude beneficial or harmful effects of one agent over the other. One RCT comparing six months' extension of anticoagulation with 18 months of ximelagatran 24 mg twice daily versus no extended ximelagatran did not exclude beneficial or harmful effects for the outcomes of reduction in VTE, mortality, and minor bleeding. One RCT comparing once-weekly subcutaneous injection of idraparinux for three or six months versus standard treatment (parenteral anticoagulation followed by warfarin or acenocoumarol) suggested a reduction in recurrent VTE (HR 0.39; 95% CI 0.14 to 1.11) at six months, but did not exclude beneficial or harmful effects for the outcomes of mortality (HR 0.99; 95% CI 0.66 to 1.48) and major bleeding (RR 1.04; 95% CI 0.39 to 2.83).
For the long-term treatment of VTE in patients with cancer, LMWH compared with VKA reduces venous thromboembolic events but not mortality. The decision for a patient with cancer and VTE to start long-term LMWH versus oral anticoagulation should balance the benefits and harms and integrate the patient's values and preferences for the important outcomes and alternative management strategies.
Background
Cancer increases the risk of thromboembolic events, especially in people receiving anticoagulation treatments.
Objectives
To compare the efficacy and safety of low molecular weight ...heparins (LMWHs), direct oral anticoagulants (DOACs), vitamin K antagonists (VKAs), and other anticoagulants for the long‐term treatment of venous thromboembolism (VTE) in people with cancer.
Search methods
We conducted a literature search including a comprehensive electronic search of the Cochrane Central Register of Controlled Trials ), MEDLINE (Ovid), and Embase (Ovid); handsearching conference proceedings; checking references of included studies; and a search for ongoing studies in trial registries. As part of the living systematic review approach, we run searches continually, incorporating new evidence after it is identified. Last search date 14 May 2021.
Selection criteria
Randomized controlled trials (RCTs) assessing the benefits and harms of long‐term treatment with LMWHs, DOACs, VKAs, or other anticoagulants in people with cancer and symptomatic VTE.
Data collection and analysis
We extracted data in duplicate on study characteristics and risk of bias. Outcomes included: all‐cause mortality, recurrent VTE, major bleeding, minor bleeding, thrombocytopenia, and health‐related quality of life (QoL). We assessed the certainty of the evidence at the outcome level following the GRADE approach (GRADE handbook GRADE handbook).
Main results
Of 3583 citations,19 RCTs fulfilled the eligibility criteria.
Low molecular weight heparins versus vitamin K antagonists Eight studies enrolling 2327 participants compared LMWHs with VKAs. Meta‐analysis of five studies probably did not rule out a beneficial or harmful effect of LMWHs compared to VKAs on mortality up to 12 months of follow‐up (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.88 to 1.13; risk difference (RD) 0 fewer per 1000, 95% CI 45 fewer to 48 more; moderate‐certainty evidence). Meta‐analysis of four studies did not rule out a beneficial or harmful effect of LMWHs compared to VKAs on major bleeding (RR 1.09, 95% CI 0.55 to 2.12; RD 4 more per 1000, 95% CI 19 fewer to 48 more, moderate‐certainty evidence) or minor bleeding (RR 0.78, 95% CI 0.47 to 1.27; RD 38 fewer per 1000, 95% CI 92 fewer to 47 more; low‐certainty evidence), or thrombocytopenia (RR 0.94, 95% CI 0.52 to 1.69). Meta‐analysis of five studies showed that LMWHs probably reduced the recurrence of VTE compared to VKAs (RR 0.58, 95% CI 0.43 to 0.77; RD 53 fewer per 1000, 95% CI 29 fewer to 72 fewer, moderate‐certainty evidence).
Direct oral anticoagulants versus vitamin K antagonists Five studies enrolling 982 participants compared DOACs with VKAs. Meta‐analysis of four studies may not rule out a beneficial or harmful effect of DOACs compared to VKAs on mortality (RR 0.93, 95% CI 0.71 to 1.21; RD 12 fewer per 1000, 95% CI 51 fewer to 37 more; low‐certainty evidence), recurrent VTE (RR 0.66, 95% CI 0.33 to 1.31; RD 14 fewer per 1000, 95% CI 27 fewer to 12 more; low‐certainty evidence), major bleeding (RR 0.77, 95% CI 0.38 to 1.57, RD 8 fewer per 1000, 95% CI 22 fewer to 20 more; low‐certainty evidence), or minor bleeding (RR 0.84, 95% CI 0.58 to 1.22; RD 21 fewer per 1000, 95% CI 54 fewer to 28 more; low‐certainty evidence). One study reporting on DOAC versus VKA was published as so is not included in the main analysis.
Direct oral anticoagulants versus low molecular weight heparins Two studies enrolling 1455 participants compared DOAC with LMWH. The study by Raskob did not rule out a beneficial or harmful effect of DOACs compared to LMWH on mortality up to 12 months of follow‐up (RR 1.07, 95% CI 0.92 to 1.25; RD 27 more per 1000, 95% CI 30 fewer to 95 more; low‐certainty evidence). The data also showed that DOACs may have shown a likely reduction in VTE recurrence up to 12 months of follow‐up compared to LMWH (RR 0.69, 95% CI 0.47 to 1.01; RD 36 fewer per 1000, 95% CI 62 fewer to 1 more; low‐certainty evidence). DOAC may have increased major bleeding at 12 months of follow‐up compared to LMWH (RR 1.71, 95% CI 1.01 to 2.88; RD 29 more per 1000, 95% CI 0 fewer to 78 more; low‐certainty evidence) and likely increased minor bleeding up to 12 months of follow‐up compared to LMWH (RR 1.31, 95% CI 0.95 to 1.80; RD 35 more per 1000, 95% CI 6 fewer to 92 more; low‐certainty evidence). The second study on DOAC versus LMWH was published as an and is not included in the main analysis.
Idraparinux versus vitamin K antagonists One RCT with 284 participants compared once‐weekly subcutaneous injection of idraparinux versus standard treatment (parenteral anticoagulation followed by warfarin or acenocoumarol) for three or six months. The data probably did not rule out a beneficial or harmful effect of idraparinux compared to VKAs on mortality at six months (RR 1.11, 95% CI 0.78 to 1.59; RD 31 more per 1000, 95% CI 62 fewer to 167 more; moderate‐certainty evidence), VTE recurrence at six months (RR 0.46, 95% CI 0.16 to 1.32; RD 42 fewer per 1000, 95% CI 65 fewer to 25 more; low‐certainty evidence) or major bleeding (RR 1.11, 95% CI 0.35 to 3.56; RD 4 more per 1000, 95% CI 25 fewer to 98 more; low‐certainty evidence).
Authors' conclusions
For the long‐term treatment of VTE in people with cancer, evidence shows that LMWHs compared to VKAs probably produces an important reduction in VTE and DOACs compared to LMWH, may likely reduce VTE but may increase risk of major bleeding. Decisions for a person with cancer and VTE to start long‐term LMWHs versus oral anticoagulation should balance benefits and harms and integrate the person's values and preferences for the important outcomes and alternative management strategies.
Editorial note: this is a living systematic review (LSR). LSRs offer new approaches to review updating in which the review is continually updated, incorporating relevant new evidence as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.
As part of an effort to develop an extension of the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 statement for living systematic reviews (LSRs), we discuss ...conceptual issues relevant to the reporting of LSRs and highlight a few challenges.
Discussion of conceptual issues based on a scoping review of the literature and discussions among authors.
We first briefly describe aspects of the LSR production process relevant to reporting. The production cycles differ by whether the literature surveillance identifies new evidence and whether newly identified evidence is judged to be consequential. This impacts the timing, content, and format of LSR versions. Second, we discuss four types of information that are specific to the reporting of LSRs: justification for adopting the living mode, LSR specific methods, changes between LSR versions, and LSR updating status. We also discuss the challenge of conveying changes between versions to the reader. Third, we describe two commonly used reporting formats of LSRs: full and partial reports. Although partial reports are easier to produce and publish, they lead to the scattering of information across different versions. Full reports ensure the completeness of reporting. We discuss the implications for the extension of the PRISMA 2020 statement for LSRs.
We argue that a dynamic publication platform would facilitate complete and timely reporting of LSRs.
Abstract Objective To provide GRADE guidance for assessing risk of bias across an entire body of evidence consequent on missing data for systematic reviews of both binary and continuous outcomes. ...Study design Systematic survey of published methodological research, iterative discussions, testing in systematic reviews, and feedback from the GRADE Working Group. Results Approaches begin with a primary meta-analysis using a complete case analysis followed by sensitivity meta-analyses imputing, in each study, data for those with missing data, and then pooling across studies. For binary outcomes we suggest use of “plausible worst case” in which review authors assume that those with missing data in treatment arms have proportionally higher event rates than those followed successfully. For continuous outcomes, imputed mean values come from other studies within the systematic review, and the standard deviation from the median standard deviations of the control arms of all studies. Conclusions If the results of the primary meta-analysis are robust to the most extreme assumptions viewed as plausible, one does not rate down certainty in the evidence for risk of bias due to missing participant outcome data. If the results prove not robust to plausible assumptions, one would rate down certainty in the evidence for risk of bias.
•13 RCTs from 2012 to 2016 examined digital push interventions on vaccination.•Digital push arms had 1.181.11,1.25 the odds of vaccination compared to controls.•Heterogeneity was high (i2 = 86%) and ...certainty of evidence was moderate to very low.•While promising, further evaluation of digital push for vaccination is warranted.
Recent outbreaks and renewed concerns about immunization coverage call for new and effective interventions to improve vaccine uptake. Digital technologies have the potential to help address both suboptimal vaccine uptake and series completion. However, the effectiveness of pushing information and reminders to patients through digital technologies to address vaccination is not known.
The aim of this study is to determine if digital push interventions are effective in increasing vaccine uptake and series completion compared to non-digital interventions.
We searched for RCTs where adults or parents of children were eligible for vaccination, the intervention was digital-push and the comparison group was non-digital. We included outcomes of vaccine uptake or series completion. We estimated summary effect sizes, heterogeneity using the χ2 test and quantified using the I2 statistic. Where heterogeneity remained significant, we conducted subgroup analyses. We assessed risk of bias, certainty of evidence and publication bias.
The search identified 159 peer-reviewed scientific publications. After review, a total of 12 manuscripts representing 13 empirical studies published between 2012 and 2016 were included. When comparing digital push interventions to non-digital ones, patients had 1.181.11,1.25 the odds of receiving vaccination or series completion compared to controls. In parents of children aged 18 and younger, those receiving digital push had a 1.221.15,1.30 increased odds compared to controls. Both analyses had high statistical heterogeneity, with I2 values of 86% and 79% respectively. The risk of bias was low with 10 of 13 studies considered low risk in five or more domains. The certainty of evidence for series completion was very low and for vaccine uptake was assessed to be moderate.
This study provides evidence that digital push technologies have a modest, positive impact on vaccine uptake and series completion compared to non-digital interventions.
Background
Oncology guidelines suggest using the Khorana score to select ambulatory cancer patients receiving chemotherapy for primary venous thromboembolism (VTE) prevention, but its performance in ...different cancers remains uncertain.
Objective
To examine the performance of the Khorana score in assessing 6‐month VTE risk, and the efficacy and safety of low‐molecular‐weight heparin (LMWH) among high‐risk Khorana score patients.
Methods
This individual patient data meta‐analysis evaluated (ultra)‐LMWH in patients with solid cancer using data from seven randomized controlled trials.
Results
A total of 3293 patients from the control groups with an available Khorana score had lung (n = 1913; 58%), colorectal (n = 452; 14%), pancreatic (n = 264; 8%), gastric (n = 201; 6%), ovarian (n = 184; 56%), breast (n = 164; 5%), brain (n = 84; 3%), or bladder cancer (n = 31; 1%). The 6‐month VTE incidence was 9.8% among high‐risk Khorana score patients and 6.4% among low‐to‐intermediate‐risk patients (odds ratio OR, 1.6; 95% confidence interval CI, 1.1‐2.2). The dichotomous Khorana score performed differently in lung cancer patients (OR 1.1; 95% CI, 0.72‐1.7) than in the group with other cancer types (OR 3.2; 95% CI, 1.8‐5.6; Pinteraction = .002). Among high‐risk patients, LMWH decreased the risk of VTE by 64% compared with controls (OR 0.36; 95% CI, 0.22‐0.58), without increasing the risk of major bleeding (OR 1.1; 95% CI, 0.59‐2.1).
Conclusion
The Khorana score was unable to stratify patients with lung cancer based on their VTE risk. Among those with other cancer types, a high‐risk score was associated with a three‐fold increased risk of VTE compared with a low‐to‐intermediate risk score. Thromboprophylaxis was effective and safe in patients with a high‐risk Khorana score.
The choice of the appropriate perioperative thromboprophylaxis in patients with cancer depends on the relative benefits and harms of low molecular weight heparin (LMWH) and unfractionated heparin ...(UFH).
To update a systematic review of the evidence for the relative efficacy and safety of LMWH and UFH for perioperative thromboprophylaxis in patients with cancer.
We performed a comprehensive search for trials of anticoagulation in patients with cancer including a February 2013 electronic search of: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE. We also handsearched conference proceedings, reviewed reference list of included studies, used the 'related citations' feature in PubMed, and searched clinicaltrials.gov for ongoing studies.
Randomized controlled trials (RCTs) that enrolled patients with cancer undergoing a surgical intervention and compared the effects of LMWH to UFH on mortality, deep venous thrombosis (DVT), pulmonary embolism (PE), bleeding outcomes, or thrombocytopenia.
Two review authors independently used a standardized form to extract in duplicate data on participants, interventions, outcomes of interest, and risk of bias. Where possible, we conducted meta-analyses using the random-effects model.
Of 9559 identified unique citations, we included 16 RCTs with 12,890 patients with cancer, all using preoperative prophylactic anticoagulation. We identified no new study with this update. The overall quality of evidence was moderate. The meta-analyses did not conclusively rule out either a beneficial or harmful effect of LMWH compared with UFH for the following outcomes: mortality (risk ratio (RR) 0.89; 95% confidence interval (CI) 0.74 to 1.08), PE (RR 0.73; 95% CI 0.34 to 1.54), symptomatic DVT (RR 0.50; 95% CI 0.20 to 1.28), asymptomatic DVT (RR 0.81; 95% CI 0.66 to 1.01),major bleeding (RR 0.85; 95% CI 0.52 to 1.37), and minor bleeding (RR 0.92; 95% CI 0.47 to 1.79). LMWH was associated with lower incidence of wound hematoma (RR 0.68; 95% CI 0.52 to 0.88) but higher volume of intraoperative transfusion (mean difference (MD) 74 mL; 95% CI 47 to 102). The meta-analyses found no statistically significant differences for any of the following outcomes: reoperation for bleeding (RR 0.72; 95% CI 0.06 to 8.48) , intraoperative blood loss (MD= -6mL; 95% CI -87 to 74), postoperative transfusion (MD= 79mL; 95% CI -54 to 211), postoperative drain volume (MD= 27mL; 95% CI -44 to 98), and thrombocytopenia (RR 1.33; 95% CI 0.59 to 3.00).
We found no difference between perioperative thromboprophylaxis with LMWH versus UFH in their effects on mortality, thromboembolic outcomes, major bleeding, or minor bleeding in patients with cancer. Further trials are needed to evaluate the benefits and harms of different heparin thromboprophylaxis strategies in this population more thoroughly.
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