Risk of Venous Thromboembolism by Cancer Type: A Network Meta-Analysis.

Patients with cancer have an increased risk of venous thromboembolism (VTE). Comparing tumor-specific VTE risk is complicated by factors such as surgery, disease stage, and chemotherapy. Network meta-analysis (NMA) using cancer types as network nodes enabled us to estimate VTE rates by leveraging comparisons across cancer types while adjusting for baseline VTE risk in individual studies. This study was conducted to estimate the risk of VTE by cancer type and factors influencing VTE risk. The Embase, MEDLINE, and Cochrane Library repositories were systematically searched to identify clinical trials and observational studies published from 2005 to 2022 that assessed the risk of primary cancer-related VTE among two or more distinct cancer types. Studies with similar cancer populations and study methods reporting VTE occurring within 1 year of diagnosis were included in the NMA. Relative VTE rates across cancer types were estimated with random-effects Bayesian NMAs. Absolute VTE rates were calculated from these estimates using the average VTE incidence in lung cancer (the most frequently reported type) as the "anchor." From 2,603 records reviewed, 30 studies were included in this NMA. The general network described 3,948,752 patients and 18 cancer types: 3.1% experienced VTE within 1 year of diagnosis, with cancer-specific rates ranging from 0.7 to 7.4%. Consistent with existing VTE risk prediction tools, pancreatic cancer was associated with higher-than-average VTE risk. Other cancer types with high VTE risk were brain and ovarian cancers. The relative rankings of VTE risk for certain cancers changed based on disease stage and/or receipt of chemotherapy or surgery.

Indirect comparisons of brigatinib and alectinib for front-line ALK-positive non-small-cell lung cancer.

Aim: To conduct an indirect treatment comparison (ITC) of the relative efficacy of brigatinib and alectinib for progression-free survival in people with tyrosine kinase inhibitor (TKI)-naive ALK-positive non-small-cell lung cancer (NSCLC). Methods: Final aggregate and patient-level data from the ALTA-1L trial comparing brigatinib to crizotinib and published aggregate data from ALEX (comparing alectinib to crizotinib) were contrasted using Bucher ITC and matching-adjusted indirect comparisons (MAICs). Results: No statistically significant differences were identified between brigatinib and alectinib in reducing the risk of disease progression overall and in patients with baseline central nervous system metastases. Conclusion: Brigatinib appeared similar to alectinib in reducing risk of disease progression for people with TKI-naive ALK-positive NSCLC.

Patients with advanced non-small-cell lung cancer (NSCLC) who have a genetic marker called rearrangement in the anaplastic lymphoma kinase, or ALK-positive disease, are treated with targeted medications taken by mouth. Two medications, alectinib and brigatinib, are both considered first-line treatment for these patients but have not been compared head-to-head. Recently, updated clinical trial results were published for these medications. The present study utilized these updated results and advanced statistical tests to indirectly compare the effectiveness of the two treatments to help guide clinical treatment choices. Results showed brigatinib and alectinib have a similar magnitude of effect in decreasing the risk of a patient with ALK-positive NSCLC developing worsening disease.

Network meta-analysis of eribulin versus other chemotherapies used as second- or later-line treatment in locally advanced or metastatic breast cancer.

BACKGROUND: Eribulin mesylate (ERI; Halaven®) is a microtubule inhibitor approved in the United States for metastatic breast cancer patients with at least two prior chemotherapy regimens for metastatic breast cancer, and in the European Union in locally advanced breast cancer or metastatic breast cancer patients who progressed after at least one chemotherapy for advanced disease. This network meta-analysis compared the efficacy and safety of ERI versus other chemotherapies in this setting. METHODS: Systematic searches conducted in MEDLINE, Embase, and the Cochrane Central Register of Clinical Trials identified randomized controlled trials of locally advanced breast cancer/metastatic breast cancer chemotherapies in second- or later-line settings. Efficacy assessment included pre-specified subgroup analysis of breast cancer subtypes. Included studies were assessed for quality using the Centre for Reviews and Dissemination tool. Bayesian network meta-analysis estimated primary outcomes of overall survival and progression-free survival using fixed-effect models. Comparators included: capecitabine (CAP), gemcitabine (GEM), ixabepilone (IXA), utidelone (UTI), treatment by physician's choice (TPC), and vinorelbine (VIN). RESULTS: The network meta-analysis included seven trials. Results showed that second- or later-line patients treated with ERI had statistically longer overall survival versus TPC (hazard ratio [HR]: 0.81; credible interval [CrI]: 0.66-0.99) or GEM+VIN (0.62; 0.42-0.90) and statistically longer progression-free survival versus TPC (0.76; 0.64-0.90), but statistically shorter progression-free survival versus CAP+IXA (1.40; 1.17-1.67) and CAP+UTI (1.61; 1.23-2.12). In triple negative breast cancer, ERI had statistically longer overall survival versus CAP (0.70; 0.54-0.90); no statistical differences in progression-free survival were observed in triple negative breast cancer. CONCLUSIONS: This network meta-analysis suggests that ERI may provide an overall survival benefit in the overall locally advanced breast cancer/metastatic breast cancer populations and triple negative breast cancer subgroup compared to standard treatments. These findings support the use of ERI in second- or later-line treatment of patients with locally advanced breast cancer/metastatic breast cancer.

The impact of intra-abdominal pressure on perioperative outcomes in laparoscopic cholecystectomy: a systematic review and network meta-analysis of randomized controlled trials.

BACKGROUND: Laparoscopic cholecystectomy involves using intra-abdominal pressure (IAP) to facilitate adequate surgical conditions. However, there is no consensus on optimal IAP levels to improve surgical outcomes. Therefore, we conducted a systematic literature review (SLR) to examine outcomes of low, standard, and high IAP among adults undergoing laparoscopic cholecystectomy. METHODS: An electronic database search was performed to identify randomized controlled trials (RCTs) that compared outcomes of low, standard, and high IAP among adults undergoing laparoscopic cholecystectomy. A Bayesian network meta-analysis (NMA) was used to conduct pairwise meta-analyses and indirect treatment comparisons of the levels of IAP assessed across trials. RESULTS: The SLR and NMA included 22 studies. Compared with standard IAP, on a scale of 0 (no pain at all) to 10 (worst imaginable pain), low IAP was associated with significantly lower overall pain scores at 24 h (mean difference [MD]: - 0.70; 95% credible interval [CrI]: - 1.26, - 0.13) and reduced risk of shoulder pain 24 h (odds ratio [OR] 0.24; 95% CrI 0.12, 0.48) and 72 h post-surgery (OR 0.22; 95% CrI 0.07, 0.65). Hospital stay was shorter with low IAP (MD: - 0.14 days; 95% CrI - 0.30, - 0.01). High IAP was not associated with a significant difference for these outcomes when compared with standard or low IAP. No significant differences were found between the IAP levels regarding need for conversion to open surgery; post-operative acute bleeding, pain at 72 h, nausea, and vomiting; and duration of surgery. CONCLUSIONS: Our study of published trials indicates that using low, as opposed to standard, IAP during laparoscopic cholecystectomy may reduce patients' post-operative pain, including shoulder pain, and length of hospital stay. Heterogeneity in the pooled estimates and high risk of bias of the included trials suggest the need for high-quality, adequately powered RCTs to confirm these findings.

Interpreting the Tests of Focal Cortical Dysplasia for Epilepsy Surgery Referral.

OBJECTIVE: Focal cortical dysplasia (FCD) is a common cause of refractory, focal onset epilepsy in children. Interictal, scalp electroencephalograph (EEG) markers have been associated with these pathologies and epilepsy surgery may be an option for some patients. We aim to study how scalp EEG and magnetic resonance imaging (MRI) markers of FCD affect referral of these patients for surgical evaluation. METHODS: A single-center, retrospective review of children with focal onset epilepsy. Patients were included if they were between 1 month and 18 years of age, had focal onset seizures, prolonged scalp EEG monitoring, and an MRI conducted after 2 years of age. Statistics were carried out using the chi-squared and student's t-test, as well as a logistic regression model. RESULTS: Sixty-eight patients were included in the study. Thirty-seven of these patients were referred to a comprehensive pediatric epilepsy program (CPEP) for surgical evaluation, and of these 22% showed FCD EEG markers, 32% FCD MRI markers, and 10% had both. These markers were also present in patients not referred to a CPEP. The MRI markers were significantly associated with CPEP referral, whereas EEG markers were not. Neither marker type was associated with epilepsy surgery. CONCLUSION: This study found that children with focal onset epilepsy were more likely to be referred for surgical evaluation if they were medically refractory, or were diagnosed with FCD or tumor on MRI. Scalp EEG markers of FCD were not associated with CPEP referral. The online tool CASES may be a useful physician guide for identifying appropriate children for epilepsy surgery referral.

Interpréter les tests de détection de la dysplasie corticale focale en vue d'une évaluation préopératoire du traitement de l'épilepsie.Objectif: La dysplasie corticale focale (DCF) constitue une des causes communes des crises convulsives partielles réfractaires chez l'enfant. À la suite d'EEG effectués au niveau du cuir chevelu, des marqueurs de l'activité épileptique interictale ont été associés avec ce trouble pour lequel une intervention chirurgicale peut constituer, dans le cas de certains patients, une option. Nous voulons nous pencher sur la façon dont ces marqueurs et les marqueurs utilisés lors d'examens d'IRM pour la DCF peuvent affecter l'aiguillage de ces patients en vue d'une évaluation préopératoire. Méthodes: Dans un seul établissement hospitalier, nous avons effectué une analyse rétrospective de cas d'enfants chez qui sont apparues des crises convulsives partielles. Pour être inclus, les patients devaient être âgés de 1 mois à 18 ans, avoir été victimes de telles crises convulsives, avoir bénéficié de surveillance prolongée par EEG et avoir subi un examen d'IRM après l'âge de deux ans. Nous avons enfin effectué une analyse statistique à l'aide d'un modèle de régression logistique et des tests du X2 et de Student. Résultats: Au total, nous avons inclus soixante-huit patients dans cette étude. Trente-sept d'entre eux ont été redirigés vers un programme pédiatrique complet de traitement de l'épilepsie (comprehensive pediatric epilepsy program) en vue d'une évaluation préopératoire. Sur ces trente-sept patients, on a observé chez 22 % d'entre eux les marqueurs électroencéphalographiques associés à la DCF ; ce pourcentage atteignait 32 % dans le cas des marqueurs de la DCF utilisés en imagerie ; enfin, on a pu détecter ces deux types de marqueurs chez 10 % de ces trente-sept patients. Fait à souligner, ces marqueurs étaient aussi présents chez des patients n'ayant pas été orientés vers le type de programme cité ci-dessus. En outre, les marqueurs utilisés en imagerie se sont avérés étroitement associés au fait d'orienter des patients vers ce programme tandis que les marqueurs électroencéphalographiques ne l'étaient pas. Finalement, aucun de ces types de marqueurs n'a pu être associé à une intervention chirurgicale visant à traiter l'épilepsie. Conclusion: Cette étude a donc permis de constater que les enfants atteints de crises convulsives partielles étaient plus susceptibles d'être orientés en vue d'une évaluation préopératoire si leur trouble était de nature réfractaire ou s'ils avaient reçu un diagnostic de DCF ou de tumeur cancéreuse à la suite d'un examend'IRM. Les marqueurs électroencéphalographiques de la DCF n'ont pas été associés à un aiguillage vers un programme pédiatrique complet de traitement de l'épilepsie. Il se pourrait à cet égard que l'outil en ligne CASES soit un guide utile pour les médecins souhaitant identifier les enfants convenant à un aiguillage en vue d'un traitement chirurgical de l'épilepsie.

Contribution of common non-synonymous variants in PCSK1 to body mass index variation and risk of obesity: a systematic review and meta-analysis with evidence from up to 331 175 individuals.

Polymorphisms rs6232 and rs6234/rs6235 in PCSK1 have been associated with extreme obesity [e.g. body mass index (BMI) ≥ 40 kg/m(2)], but their contribution to common obesity (BMI ≥ 30 kg/m(2)) and BMI variation in a multi-ethnic context is unclear. To fill this gap, we collected phenotypic and genetic data in up to 331 175 individuals from diverse ethnic groups. This process involved a systematic review of the literature in PubMed, Web of Science, Embase and the NIH GWAS catalog complemented by data extraction from pre-existing GWAS or custom-arrays in consortia and single studies. We employed recently developed global meta-analytic random-effects methods to calculate summary odds ratios (OR) and 95% confidence intervals (CIs) or beta estimates and standard errors (SE) for the obesity status and BMI analyses, respectively. Significant associations were found with binary obesity status for rs6232 (OR = 1.15, 95% CI 1.06-1.24, P = 6.08 × 10(-6)) and rs6234/rs6235 (OR = 1.07, 95% CI 1.04-1.10, P = 3.00 × 10(-7)). Similarly, significant associations were found with continuous BMI for rs6232 (ß = 0.03, 95% CI 0.00-0.07; P = 0.047) and rs6234/rs6235 (ß = 0.02, 95% CI 0.00-0.03; P = 5.57 × 10(-4)). Ethnicity, age and study ascertainment significantly modulated the association of PCSK1 polymorphisms with obesity. In summary, we demonstrate evidence that common gene variation in PCSK1 contributes to BMI variation and susceptibility to common obesity in the largest known meta-analysis published to date in genetic epidemiology.

Examining the provisional guidelines for weight gain in twin pregnancies: a retrospective cohort study.

BACKGROUND: Weight gain during pregnancy has an important impact on maternal and neonatal health. Unlike the Institute of Medicine (IOM) recommendations for weight gain in singleton pregnancies, those for twin gestations are termed "provisional", as they are based on limited data. The objectives of this study were to determine the neonatal and maternal outcomes associated with gaining weight below, within and above the IOM provisional guidelines on gestational weight gain in twin pregnancies, and additionally, to explore ranges of gestational weight gain among women who delivered twins at the recommended gestational age and birth weight, and those who did not. METHODS: A retrospective cohort study of women who gave birth to twins at ≥20 weeks gestation, with a birth weight ≥ 500 g was conducted in Nova Scotia, Canada (2003-2014). Our primary outcome of interest was small for gestational age (<10th percentile). In order to account for gestational age at delivery, weekly rates of 2nd and 3rd trimester weight gain were used to categorize women as gaining below, within, or above guidelines. We performed traditional regression analyses for maternal outcomes, and to account for the correlated nature of the neonatal outcomes in twins, we used generalized estimating equations (GEE). RESULTS: A total of 1482 twins and 741 mothers were included, of whom 27%, 43%, and 30% gained below, within, and above guidelines, respectively. The incidence of small for gestational age in these three groups was 30%, 21%, and 20%, respectively, and relative to gaining within guidelines, the adjusted odds ratios were 1.44 (95% CI 1.01-2.06) for gaining below and 0.92 (95% CI 0.62-1.36) for gaining above. The gestational weight gain in women who delivered twins at 37-42 weeks with average birth weight ≥ 2500 g and those who delivered twins outside of the recommend ranges were comparable to each other and the IOM recommendations. CONCLUSIONS: While gestational weight gain below guidelines for twins was associated with some adverse neonatal outcomes, additional research exploring alternate ranges of gestational weight gain in twin pregnancies is warranted, in order to optimize neonatal and maternal outcomes.

Live Attenuated Versus Inactivated Influenza Vaccine in Hutterite Children: A Cluster Randomized Blinded Trial.

BACKGROUND: Whether vaccinating children with intranasal live attenuated influenza vaccine (LAIV) is more effective than inactivated influenza vaccine (IIV) in providing both direct protection in vaccinated persons and herd protection in unvaccinated persons is uncertain. Hutterite colonies, where members live in close-knit, small rural communities in which influenza virus infection regularly occurs, offer an opportunity to address this question. OBJECTIVE: To determine whether vaccinating children and adolescents with LAIV provides better community protection than IIV. DESIGN: A cluster randomized blinded trial conducted between October 2012 and May 2015 over 3 influenza seasons. (ClinicalTrials.gov: NCT01653015). SETTING: 52 Hutterite colonies in Alberta and Saskatchewan, Canada. PARTICIPANTS: 1186 Canadian children and adolescents aged 36 months to 15 years who received the study vaccine and 3425 community members who did not. INTERVENTION: Children were randomly assigned according to community in a blinded manner to receive standard dosing of either trivalent LAIV or trivalent IIV. MEASUREMENTS: The primary outcome was reverse transcriptase polymerase chain reaction-confirmed influenza A or B virus in all participants (vaccinated children and persons who did not receive the study vaccine). RESULTS: Mean vaccine coverage among children in the LAIV group was 76.9% versus 72.3% in the IIV group. Influenza virus infection occurred at a rate of 5.3% (295 of 5560 person-years) in the LAIV group versus 5.2% (304 of 5810 person-years) in the IIV group. The hazard ratio comparing LAIV with IIV for influenza A or B virus was 1.03 (95% CI, 0.85 to 1.24). LIMITATION: The study was conducted in Hutterite communities, which may limit generalizability. CONCLUSION: Immunizing children with LAIV does not provide better community protection against influenza than IIV. PRIMARY FUNDING SOURCE: The Canadian Institutes for Health Research.

Treatment of idiopathic pulmonary fibrosis: a network meta-analysis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease associated with high morbidity and mortality. Effective treatments for IPF are limited. Several recent studies have investigated novel therapeutic agents for IPF, but very few have addressed their comparative benefits and harms. METHODS: We performed a Bayesian network meta-analysis (NMA) to assess the effects of different treatments for IPF on mortality and serious adverse events (SAEs). We searched MEDLINE and EMBASE for randomized controlled trials (RCTs) up to August 2015. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach served to assess the certainty in the evidence of direct and indirect estimates. We calculated the surface under the cumulative ranking curve (SUCRA) for each treatment. We included parallel group RCTs, including factorial designs, but excluded quasi-randomized and cross-over trials. Studies were only included if they involved adult (≥18 years of age) patients with IPF as defined by the 2011 criteria and examined one of the 10 interventions of interest (ambrisentan, bosentan, imatinib, macitentan, N-acetylcysteine, nintedanib, pirfenidone, sildenafil, prednisone/azathioprine/N-acetylcysteine triple therapy, and vitamin K antagonist). RESULTS: A total of 19 RCTs (5,694 patients) comparing 10 different interventions with placebo and an average follow-up period of 1 year fulfilled the inclusion criteria. SUCRA analysis suggests nintedanib, pirfenidone, and sildenafil are the three treatments with the highest probability of reducing mortality in IPF. Indirect comparison showed no significant difference in mortality between pirfenidone and nintedanib (NMA OR, 1.05; 95% CrI, 0.45-2.78, moderate certainty of evidence), pirenidone and sildenafil (NMA OR, 2.26; 95% CrI, 0.44-13.17, low certainty of evidence), or nintedanib and sildenafil (NMA OR 2.40; 95% CrI, 0.47-14.66, low certainty of evidence). Sildenafil, pirfenidone, and nintedanib were ranked second, fourth, and sixth out of 10 for SAEs. CONCLUSION: In the absence of direct comparisons between treatment interventions, this NMA suggests that treatment with nintedanib, pirfenidone, and sildenafil extends survival in patients with IPF. The SAEs of these agents are similar to the other interventions and include mostly dermatologic and gastrointestinal manifestations. Head-to-head comparisons need to confirm these findings.

Why Are Half of Women Interested in Participating in Group Prenatal Care?

OBJECTIVE: To determine the likelihood of participating in group prenatal care (GPC) and associated factors among low-risk women receiving traditional prenatal care from obstetricians, family physicians or midwives, and to determine factors associated with likelihood of participating. METHODS: Prior to completing a self-administered questionnaire, a 2-min compiled video of GPC was shown to pregnant women receiving traditional prenatal care. Data were collected on opinions of current prenatal care, GPC, and demographics. Biologically plausible variables with a p value ≤0.20 were entered in the multivariable logistic regression model and those with a p value <0.05 were retained. RESULTS: Of 477 respondents, 234 [49.2%, 95% confidence interval (CI) 44.6-53.6%] reported being "definitely" or "probably likely" to participate in GPC. Women were more likely to participate in GPC if they had at least postsecondary education [adjusted odds ratio (aOR) 1.84, 95% CI 1.05-3.24], had not discussed labour with their care provider (aOR 1.67, 95% CI 1.12-2.44), and valued woman-centeredness ("fairly important" aOR 2.81, 95% CI 1.77-4.49; "very important" aOR 4.10, 95% CI 2.45-6.88). Women placed high importance on learning components of GPC. The majority would prefer to be with similar women, especially in age. About two-thirds would prefer to have support persons attend GPC and over half would be comfortable with male partners. CONCLUSION: Approximately half of women receiving traditional prenatal care were interested in participating in GPC. Our findings will hopefully assist providers interested in optimizing satisfaction with traditional prenatal care and GPC by identifying important elements of each, and thus help engage women to consider GPC.

Knowledge translation tool to improve pregnant women's awareness of gestational weight gain goals and risks of gaining outside recommendations: a non-randomized intervention study.

BACKGROUND: There is an urgent need to prevent excessive pregnancy weight gain, a contributor to both maternal and child obesity. However, the majority of women had reported not being counseled to gain an appropriate amount of gestational weight by their health care providers. We developed a knowledge translation (KT) tool designed to facilitate the clinical interaction between pregnant women and their health care providers (HCPs). We piloted the tool on the impact on women's knowledge of gestational weight gain (GWG) goals, and evaluated its potential in promoting appropriate knowledge about GWG within the 2009 Institute of Medicine guidelines. METHODS: We conducted a prospective cohort study, comparing women's knowledge about GWG after the KT tool to women from the same clinics and care providers the year prior. Our primary outcome was the proportion of women who reported receiving an appropriate GWG recommendation from their care provider. We evaluated knowledge on a survey conducted at enrollment in the cohort at ≤ 20 weeks gestation and evaluated participant satisfaction with the KT tool in the third trimester. We performed univariate and multivariable logistic regression analyses for differences in outcomes with historical controls from the same clinics. Our a priori sample size calculation required 130 participants to demonstrate a 15% increase in reported counseling about gestational weight gain. RESULTS: One hundred and forty-six women were recruited and 131 (90%) completed the enrollment survey. Women who received the KT tool were more likely to report receiving a specific GWG recommendation from their HCP (adjusted odds ratio [AOR] 3.45, 95% confidence interval [CI] 2.22-5.37) and discussing GWG topics with their HCP (AOR 7.96, 95% CI 4.41-14.37), and believing that there were risks to their infants with inadequate GWG (AOR 2.48, 95% CI 1.14-5.37). Half of women (49.5%) indicated that they would recommend the tool to a friend. CONCLUSIONS: Women who received the KT tool reported receiving more counseling on GWG from their HCPs and were more aware of the risks of gaining outside appropriate GWG recommendations. The association between GWG education and GWG requires further research.

Factors Associated With Women's Plans to Gain Weight Categorized as Above or Below the National Guidelines During Pregnancy.

OBJECTIVE: Given that planning to gain gestational weight categorized as above the national guidelines is associated with actually gaining above the guidelines, we sought to identify physical, lifestyle, knowledge, and psychological factors associated with planned weight gain. METHODS: Using a piloted, self-administered questionnaire, a cross-sectional study of women with singleton pregnancies was conducted. Women's plans for weight gain were categorized as above, within, or below the guidelines. Univariate and multivariate analyses were performed. RESULTS: The response rate was 90.7% (n = 330). Compared with women whose plans to gain weight were within the guidelines, women whose plans to gain were above the guidelines were more likely to be older (adjusted odds ratio [aOR] 1.09 per year; 95% CI 1.03 to 1.16), to have a greater pre-pregnancy BMI (aOR 1.17 per unit of BMI; 95% CI 1.10 to 1.25), to drink more than one glass of soft drink or juice per day (aOR 2.73; 95% CI 1.27 to 5.87), and to report receiving a recommendation by their care provider to gain weight above the guidelines (aOR 5.46; 95% CI 1.56 to 19.05). Women whose plans to gain weight were categorized as below the guidelines were more likely to eat lunch in front of a screen (aOR 2.27; 95% CI 1.11 to 4.66) and to aspire to greater social desirability (aOR 2.51; 95% CI 1.01 to 6.22). CONCLUSION: Modifiable factors associated with planned gestational weight gain categorized as above the guidelines included soft drink or juice consumption and having a recommendation from a care provider, while planned weight gain categorized as below the guidelines was associated with eating lunch in front of a screen and social desirability.

Objectif : Puisque le fait de planifier l'atteinte d'un poids gestationnel classé comme étant supérieur à ce que recommandent les lignes directrices nationales est en fait associé à l'atteinte d'un tel poids, nous avons cherché à identifier les facteurs physiques, liés au mode de vie, liés aux connaissances et psychologiques qui sont associés au gain pondéral planifié. Méthodes : Au moyen d'un questionnaire auto-administré (ayant fait l'objet d'un projet pilote), une étude transversale a été menée auprès de femmes connaissant une grossesse monofœtale. Les plans de ces femmes quant au gain pondéral ont été classés en fonction de leur relation avec les lignes directrices (gain supérieur à ce que recommandent celles-ci, gain respectant les recommandations de celles-ci ou gain inférieur à ce que recommandent celles-ci). Des analyses univariées et multivariées ont été menées. Résultats : Le taux de réponse a été de 90,7 % (n = 330). Par comparaison avec les femmes qui planifiaient un gain pondéral respectant les recommandations des lignes directrices, les femmes qui planifiaient un gain pondéral supérieur à ce que recommandent les lignes directrices étaient plus susceptibles d'être plus âgées (rapport de cotes corrigé [RCc], 1,09 par année; IC à 95 %, 1,03 - 1,16), de présenter un IMC prégrossesse supérieur (RCc, 1,17 par unité d'IMC; IC à 95 %, 1,10 - 1,25), de boire plus d'un verre de boisson gazeuse ou de jus par jour (RCc, 2,73; IC à 95 %, 1,27 - 5,87) et de signaler que leur fournisseur de soins leur avait recommandé un gain pondéral supérieur à ce que recommandent les lignes directrices (RCc, 5,46; IC à 95 %, 1,56 - 19,05). Les femmes qui planifiaient un gain pondéral inférieur à ce que recommandent les lignes directrices étaient plus susceptibles de manger devant un écran (RCc, 2,27; IC à 95 %, 1,11 - 4,66) et d'aspirer à une désirabilité sociale plus importante (RCc, 2,51; IC à 95 %, 1,01 - 6,22). Conclusion : Parmi les facteurs modifiables qui sont associés à la planification d'un gain pondéral supérieur à ce que recommandent les lignes directrices, on trouvait la consommation de boissons gazeuses ou de jus et le fait de disposer d'une recommandation en ce sens de la part d'un fournisseur de soins; la planification d'un gain pondéral inférieur à ce que recommandent les lignes directrices était quant à elle associée au fait de manger devant un écran et à la désirabilité sociale.

What psychological, physical, lifestyle, and knowledge factors are associated with excess or inadequate weight gain during pregnancy? A cross-sectional survey.

OBJECTIVE: Excess weight gain during pregnancy is associated with increased risks of overweight and obesity in both women and their children. Conversely, inadequate weight gain can predispose to growth restriction, which is also associated with childhood obesity. Because most pregnant women now gain more weight than is recommended in guidelines and a substantial portion gain less than the recommended amounts, we sought to determine factors associated with inappropriate weight gain, including physical, lifestyle, knowledge, and particularly psychological factors. METHODS: We conducted a self-administered cross-sectional survey of English-speaking women with a live, singleton gestation. Biologically relevant variables significant at P < 0.10 were included in multiple logistic regression. RESULTS: Three hundred thirty women completed the survey, a response rate of 90.7%. Gaining weight above the amount recommended in guidelines was associated with planning to do so (adjusted OR [aOR] 11.18; 95% CI 4.45 to 28.06), bedtime television (aOR 2.38; 95% CI 1.08 to 5.23), and higher emotional instability scores (aOR 1.26; 95% CI 1.10 to 1.44). Inadequate weight gain was associated with less satisfaction with body weight (aOR 4.84; 95% CI 1.56 to 15.02) and bedtime television (aOR 3.92; 95% CI 1.50 to 10.30), while self-efficacy towards healthy weight was protective (aOR 0.91; 95% CI 0.83 to 0.99). CONCLUSION: Planned weight gain was most strongly associated with excess gestational weight gain, followed by bedtime television watching and emotional instability, while inadequate gain was associated with less satisfaction with body weight and bedtime television watching. Better characterization of psychological and other factors that predict inappropriate gain will be critical for providing a basis for interventions.

Objectif : Le gain pondéral excessif pendant la grossesse est associé à une hausse des risques de surcharge pondérale et d'obésité tant chez la femme que chez l'enfant. À l'inverse, un gain pondéral inadéquat peut prédisposer le fœtus à un retard de croissance, lequel est également associé à l'obésité infantile. Puisque, de nos jours, la plupart des femmes enceintes gagnent plus de poids que ce que recommandent les lignes directrices et qu'une partie substantielle d'entre elles gagnent, au contraire, moins de poids que ce qui est recommandé, nous avons cherché à déterminer les facteurs qui sont associés à un gain pondéral inapproprié, y compris les facteurs liés au mode de vie, liés aux connaissances, physiques et particulièrement psychologiques. Méthodes : Nous avons demandé à des femmes anglophones connaissant une grossesse monofœtale vivante de répondre à un questionnaire transversal autoadministré. Les variables biologiques pertinentes s'étant avérées significatives à P < 0,10 ont été incluses dans la régression logistique multiple. Résultats : Trois cent trente femmes ont répondu au questionnaire, ce qui représente un taux de réponse de 90,7 %. Le gain pondéral excédant les recommandations établies par les lignes directrices a été associé à l'intention de gagner du poids (RC corrigé [RCc], 11,18; IC à 95 %, 4,45 - 28,06), au fait de regarder la télévision au coucher (RCc, 2,38; IC à 95 %, 1,08 - 5,23) et aux scores accrus d'instabilité affective (RCc, 1,26; IC à 95 %, 1,10 - 1,44). Le gain pondéral inadéquat a été associé à une satisfaction moindre envers le poids corporel (RCc, 4,84; IC à 95 %, 1,56 - 15,02) et au fait de regarder la télévision au coucher (RCc, 3,92; IC à 95 %, 1,50 - 10,30), tandis que l'auto-efficacité en matière de poids santé conférait un effet protecteur (RCc, 0,91; IC à 95 %, 0,83 - 0,99). Conclusion : Le fait de planifier un gain pondéral a été le facteur le plus fortement associé à l'obtention d'un gain pondéral gestationnel excessif, le fait de regarder la télévision au coucher et l'instabilité affective constituant les deuxième et troisième facteurs en importance. Quant à lui, le gain pondéral inadéquat a été associé à une satisfaction moindre envers le poids corporel et au fait de regarder la télévision au coucher. L'obtention d'une meilleure caractérisation des facteurs psychologiques et autres qui permettent de prédire le gain pondéral inapproprié sera d'une importance cruciale pour ce qui est de la détermination des fondements de l'intervention.

Longitudinal study of influenza molecular viral shedding in Hutterite communities.

BACKGROUND: The nature of influenza viral shedding during naturally acquired infection is not well understood. METHODS: A cohort study was conducted in Hutterite colonies in Alberta, Canada. Flocked nasal swabs were collected during 3 influenza seasons (2007-2008 to 2009-2010) from both symptomatic and asymptomatic individuals infected with influenza. Samples were tested by real-time reverse-transcription polymerase chain reaction for influenza A and influenza B, and the viral load (VL) was determined for influenza A positive samples. RESULTS: Eight hundred thirty-nine participants were included in the cohort; 25% (208) tested positive for influenza viruses. They experienced 238 episodes of viral shedding, of which 23 (10%) were not accompanied by symptoms. For seasonal and pandemic H1N1, VL peaked at or before onset of acute respiratory infection. For H3N2, VL peaked 2 days after the onset of acute respiratory infection, which corresponded to peaks in systemic and respiratory symptom scores. Although the duration of shedding was shorter for asymptomatic participants, the peak level of VL shedding was similar to that of symptomatic participants. Viral loads for children and adults revealed similar patterns. CONCLUSIONS: Molecular viral shedding values follow symptom scores, but timing of peak VL varies by subtype. Asymptomatic infections are infrequent.

Predictive value of quantitative fetal fibronectin for spontaneous preterm birth in asymptomatic pregnancies: a systematic literature review and meta-analysis.

OBJECTIVE: Tests capable of accurate prediction of spontaneous preterm birth (sPTB) are crucial to inform clinical decisions to prevent neonatal deaths and reduce the risk of morbidity in surviving infants. A systematic literature review and meta-analysis were performed to assess the utility of the quantitative fetal fibronectin (fFN) test to predict sPTB at different test concentration thresholds. METHODS: Literature searches were conducted in MEDLINE, Embase, and the Cochrane Library in May 2022. Observational studies and clinical trials investigating the clinical utility of the quantitative fFN test in asymptomatic pregnancies prior to 37 weeks of gestation were eligible for inclusion. Meta-analysis quantified the risk of sPTB prior to four gestational age milestones (<28, <30, <34 and <37 weeks) based on quantitative fFN levels. No risk of bias assessment was performed however, clinical and methodological heterogeneity was explored to determine the feasibility of performing analyses. RESULTS: 11 studies showed a quantitative assessment of fFN can differentiate between very high and very low risks of sPTB in asymptomatic pregnancies with <10% of women with very low fFN (<10 ng/mL) versus 37-67% of women with very high fFN (>200 ng/mL) delivering before 34 weeks. A meta-analysis of two studies showed, albeit with a low number of events, the odds of sPTB prior to 28 weeks was nine times higher in women testing positive at ≥50 ng/mL, whereas the odds of sPTB was 25 times higher in women with fFN concentrations >200 ng/mL (versus <50 ng/mL reference). Similarly, pooling three studies showed the odds of sPTB prior to 37 weeks was four times higher in women who tested positive at ≥50 ng/ml whereas the odds of delivery before 37 weeks was seven times higher for women with fFN concentrations ≥200 ng/ml (versus <50 ng/mL reference). CONCLUSION: Quantitative fFN testing demonstrates increased predictive capabilities and utility of fFN testing in clinical practice, potentially preventing unnecessary intervention for women at very low risk and allowing an opportunity to optimize the management of asymptomatic patients at high risk of preterm delivery.

Risk of Adverse Events Associated with Domperidone and Metoclopramide in Gastroparesis: Systematic Review and Meta-analysis.

BACKGROUND: Dopamine antagonists are the main pharmacological options to treat gastroparesis. The aim of this study was to conduct a systematic literature review (SLR) to evaluate the profile of adverse events (AEs) of dopamine antagonists used in the treatment of children and adults with gastroparesis. METHODS: We searched EMBASE and MEDLINE up to March 25, 2021, for relevant clinical trials and observational studies. We conducted a proportional meta-analysis to estimate the pooled occurrence of AEs (%), with 95% confidence interval (CI), from arm-level data across studies and the comparative occurrence of AEs from placebo-controlled clinical trials (odds ratio [OR] with 95% CI). RESULTS: We identified 28 studies assessing AEs experienced by patients treated for gastroparesis with domperidone and metoclopramide; 22 studies contributed data to the meta-analyses. Cardiovascular, neurological, and endocrine AEs were commonly observed, with point incidences varying from 1 to > 50%. Clinically important AEs, such as QTc prolongation, occurred in 5% of patients treated with domperidone (95% CI: 3.32-8.62). Restlessness, an extrapyramidal AE, occurred in 15% of patients (95% CI: 7.48-26.61) treated with metoclopramide, with a 7-fold increase compared with patients receiving placebo (OR: 7.72; 95% CI: 1.27-47.05). Variation in terminology to describe extrapyramidal events precluded further pooled analyses. Additional meta-analyses were not feasible due to discrepancies in the assessment and reporting of the AEs. CONCLUSIONS: The evidence confirms concerns of cardiovascular, extrapyramidal, and endocrine AEs in patients with gastroparesis treated with domperidone and metoclopramide. Imprecise AE reporting limits firm interpretation and conclusions. REGISTRATION: PROSPERO international prospective register of systematic reviews (registration number: CRD42021248888).

Handling related publications reporting real-world evidence in network meta-analysis: a case study in multiple sclerosis.

Aim: The presence of two or more publications that report on overlapping patient cohorts poses a challenge for quantitatively synthesizing real-world evidence (RWE) studies. Thus, we evaluated eight approaches for handling such related publications in network meta-analyses (NMA) of RWE studies. Methods: Bayesian NMAs were conducted to estimate the annualized relapse rate (ARR) of disease-modifying therapies in multiple sclerosis. The NMA explored the impact of hierarchically selecting one pivotal study from related publications versus including all of them while adjusting for correlations. Results: When selecting one pivotal study from related publications, the ARR ratios were mostly similar regardless of the pivotal study selected. When including all related publications, there were shifts in the point estimates and the statistical significance. Conclusion: An a priori hierarchy should guide the selection among related publications in NMAs of RWE. Sensitivity analyses modifying the hierarchy should be considered for networks with few or small studies.

Comparative Efficacy of Biologic Disease-Modifying Anti-Rheumatic Drugs for Non-Radiographic Axial Spondyloarthritis: A Systematic Literature Review and Bucher Indirect Comparisons.

INTRODUCTION: Biologic disease-modifying anti-rheumatic drugs (bDMARDs), including certolizumab pegol (CZP), are effective treatment options for the management of non-radiographic spondyloarthritis (nr-axSpA). In the absence of head-to-head comparisons in nr-axSpA, we conducted a systematic literature review (SLR) and indirect treatment comparison (ITC) to better understand the comparative efficacy of CZP vs. other bDMARDs. METHODS: Literature searches were conducted in October 2020 in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials in patients with nr-axSpA who had failed at least one non-steroidal anti-inflammatory drug and were treated with bDMARDs. Outcomes of interest included the Assessment of Spondyloarthritis international Society (ASAS), Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Functional Index (BASFI) and Disease Activity Index (BASDAI), and spinal pain score. Comparative efficacy was examined using a series of Bucher ITCs in subgroups matched by prior exposure to bDMARDs, disease duration, baseline C-reactive protein (CRP) levels/magnetic resonance imaging (MRI) status, and timepoints, to ensure comparability between studies. RESULTS: At 12-16 weeks, treatment with CZP was significantly more likely to achieve ASAS20/40 response and ASDAS-inactive disease status vs. etanercept (ETN), ixekizumab (IXE), and secukinumab (SEC). CZP showed statistically significant improvement in BASDAI, BASFI, and total spine pain score over adalimumab (ADA), ETN, and IXE, and in BASFI over SEC. Among patients with objective signs of inflammation (OSI; elevated CRP levels and/or inflammation on MRI at baseline), CZP had a statistically significant advantage over ETN and SEC (with or without loading dose) in achieving ASAS40, whereas the comparisons with other bDMARDs did not show any statistically significant differences. CONCLUSION: In the overall matched population, CZP performed significantly better than most comparators in improving the clinical outcomes. Among patients with OSI, CZP was found to be superior to SEC (in the MRI-/CRP + and MRI + /CRP- subgroups) and ETN (in the MRI + /CRP- subgroup) and it was comparable to golimumab and IXE across the different OSI subgroups.

Belimumab versus anifrolumab in adults with systemic lupus erythematosus: an indirect comparison of clinical response at 52 weeks.

OBJECTIVE: To generate comparative efficacy evidence of belimumab versus anifrolumab in SLE that can inform treatment practices. METHODS: The SLE Responder Index (SRI)-4 response at 52 weeks of belimumab versus anifrolumab was evaluated with an indirect treatment comparison. The evidence base consisted of randomised trials that were compiled through a systemic literature review.A feasibility assessment was performed to comprehensively compare the eligible trials and to determine the most appropriate indirect treatment comparison analysis method. A multilevel network meta-regression (ML-NMR) was implemented that adjusted for differences across trials in four baseline characteristics: SLE Disease Activity Index-2K, anti-double-stranded DNA antibody positive, low complement (C)3 and low C4. Additional analyses were conducted to explore if the results were robust to different sets of baseline characteristics included for adjustment, alternative adjustment methods and changes to the trials included in the evidence base. RESULTS: The ML-NMR included eight trials: five belimumab trials (BLISS-52, BLISS-76, NEA, BLISS-SC, EMBRACE) and three anifrolumab trials (MUSE, TULIP-1, TULIP-2). Belimumab and anifrolumab were comparable in terms of SRI-4 response (OR (95% credible interval), 1.04 (0.74-1.45)), with the direction of the point estimate slightly favouring belimumab. Belimumab had a 0.58 probability of being the more effective treatment. The results were highly consistent across all analysis scenarios. CONCLUSIONS: Our results suggest that the SRI-4 response of belimumab and anifrolumab are similar at 52 weeks in the general SLE population, but the level of uncertainty around the point estimate means we cannot rule out the possibility of a clinically meaningful benefit for either treatment. It remains to be seen if specific groups of patients could derive a greater benefit from anifrolumab or from belimumab, and there is certainly an unmet need to identify robust predictors towards more personalised selection of available biological agents in SLE.

Meta-Regression of Herpes Zoster Incidence Worldwide.

INTRODUCTION: Many studies have been conducted worldwide to estimate herpes zoster (HZ) incidence rates. We synthesized studies of HZ incidence rates in the general population using meta-analysis models. METHODS: A random effects meta-analysis was conducted to estimate HZ incidence from a published worldwide systematic literature review (SLR) including only individuals aged 50 years and older. Meta-regression was used to explore whether variability in incidence rates could be explained by a combination of study-specific characteristics including age, gender, continent and year of study data. The impact of adding additional covariates-case detection method (general practitioner surveillance, healthcare database, sentinel network, etc.), case definition (medical record-based, self-reported), study design (retrospective passive surveillance, retrospective active surveillance, etc.), incidence type (cumulative incidence/1000 persons or incidence rate/1000 person-years), patient type (outpatients or in- and out-patients) and latitude to the base model-was also assessed. RESULTS: Sixty-one records from 59 studies were included in the analysis: 25, 20, 11 and 5 from Europe, North America, Asia and Oceania, respectively. There was variation in study methodology and outcomes. Heterogeneity of incidence rates was greatest among studies conducted in Asia. Meta-analysis showed that incidence increased with age, was lower in males compared to females, tended to be lower in Europe and North America compared to Asia and Oceania and increased with year of study data. The data-driven meta-regression model included continent, year of study data, gender, age and an age × gender interaction term. The difference in incidence between males and females was greater in younger ages (e.g., 50-59) compared to older age groups (e.g., 80+). None of the additional covariates contributed significantly to the model. CONCLUSION: Incidence rates were shown to vary by age, gender, continent and year of study data.