BACKGROUND: Pertussis vaccination in pregnancy has been introduced in an increasing number of countries to better protect infants against the disease in their first weeks of life. The optimal timing of pertussis vaccination in pregnancy is however still under debate.
METHODS: We systematically reviewed published literature on safety, immunogenicity and effectiveness of pertussis vaccination in pregnancy related to timing of vaccination. The search was conducted using PubMed, MEDLINE and Web of Science and yielded 1623 articles, thereof 777 duplicates. Screening resulted in the inclusion of 45 publications reporting on safety (n = 11), immunogenicity (n = 26) and/or effectiveness (n = 9). We also mapped pertussis recommendations in pregnancy by government institutions globally according to the recommended timing of vaccination.
RESULTS: Overall, the selected publications did not indicate increased safety concerns associated with timing of pertussis vaccination in pregnancy. Immunogenicity studies often suggested optimal protection at birth after early third trimester vaccination. Few studies investigated qualitative antibody characteristics, and none investigated antibody titers in breastmilk or cellular-mediated immunity related to timing of vaccination. Effectiveness studies showed decreased vaccine effectiveness of late third trimester pertussis vaccination compared to vaccination earlier in pregnancy. Worldwide, a general recommendation for pertussis vaccination in pregnancy was found for 58 countries, with as many as 22 different recommended timings registered.
CONCLUSIONS: The timing of pertussis vaccination in pregnancy seems to impact immunogenicity and vaccine effectiveness, with optimal immune responses at birth suggested following early third trimester vaccination and reduced vaccine effectiveness of late third trimester pertussis vaccination suggested compared to vaccination earlier in pregnancy. However, inconsistent and lacking data are reflected in the divergent national recommendations for pertussis vaccination in pregnancy worldwide.
CONCLUSIONS: Pertussis vaccination in pregnancy aims to protect infants in their first weeks of life. Our review suggests that immunogenicity and vaccine effectiveness are impacted by the timing of vaccination in pregnancy. National recommendations for pertussis vaccination in pregnancy vary widely worldwide.

OBJECTIVE: This study aimed (1) to assess the association between the length of the third stage of labor and adverse maternal outcome after vaginal birth and (2) to evaluate whether earlier manual placenta removal reduces the risk of adverse outcome.
METHODS: PubMed, MEDLINE, Embase, ClinicalTrials.gov, the Cochrane Library, Journals@Ovid, and the World Health Organization International Clinical Trials Registry were searched from January 1, 2000, to June 13, 2023.
METHODS: All studies that assessed adverse maternal outcome, defined as any maternal complication after vaginal birth, concerning the length of the third stage of labor and the timing of manual placenta removal were included.
METHODS: The included studies were evaluated using the Conducting Systematic Reviews and Meta-Analyses of Observational Studies of Etiology methodology. Pooled odds ratios with 95% confidence intervals were calculated. Heterogeneity (I2 test) was assessed, subgroup analyses were performed, and 95% prediction intervals were calculated.
RESULTS: To meet the first objective, 18 cohort studies were included. The assessed cutoff values for the length of the third stage of labor were 15, 30, and 60 minutes. Women with a third stage of labor of ≥15 minutes had an increased risk of postpartum hemorrhage compared with those with a third stage of labor of <15 minutes (odds ratio, 5.55; 95% confidence interval, 1.74-17.72). For women without risk factors for postpartum hemorrhage, the odds ratio was 2.20 (95% confidence interval, 0.75-6.49). Among women with a third stage of labor of ≥60 minutes vs women with a third stage of labor of <60 minutes, the odds ratio was 3.72 (95% confidence interval, 2.36-5.89). The incidence of red blood cell transfusion was higher for a third stage of labor of ≥30 minutes than for a third stage of labor of <30 minutes (odds ratio, 3.23; 95% confidence interval, 2.26-4.61). Of note, 3 studies assessed the timing of placenta removal and the risk of adverse maternal outcome. However, the results could not be pooled because of the different outcome measures. Moreover, 1 randomized controlled trial (RCT) reported a significantly higher incidence of hemodynamic compromise in women with manual placenta removal at 15 minutes than in women with manual placenta removal at 10 minutes (30/156 [19.2%] vs 10/156 [6.4%], respectively), whereas 2 observational studies reported a lower risk of bleeding among women without manual placenta removal.
CONCLUSIONS: Although the risk of adverse maternal outcome after vaginal birth increases when the third stage of labor exceeds 15 minutes, there is no convincing supporting evidence that reducing the length of the third stage of labor by earlier manual removal of the placenta can reduce the incidence of adverse maternal outcome.

BACKGROUND: Vasopressor administration at an appropriate time is crucial, but the optimal timing remains controversial.
OBJECTIVE: Does early vs late norepinephrine administration impact the prognosis of septic shock?
METHODS: Searches were conducted on PubMed, EMBASE, the Cochrane Library, and KMBASE. We included studies of adults with sepsis and categorized patients into an early and late norepinephrine group according to specific time points or differences in norepinephrine use protocols. The primary outcome was overall mortality. The secondary outcomes included length of stay in the ICU, days free from ventilator use, days free from renal replacement therapy, days free from vasopressor use, adverse events, and total fluid volume.
RESULTS: Twelve studies (four randomized controlled trials [RCTs] and eight observational studies) comprising 7,281 patients were analyzed. For overall mortality, no significant difference was found between the early norepinephrine group and late norepinephrine group in RCTs (OR, 0.70; 95% CI, 0.41-1.19) or observational studies (OR, 0.83; 95% CI, 0.54-1.29). In the two RCTs without a restrictive fluid strategy that prioritized vasopressors and lower IV fluid volumes, the early norepinephrine group showed significantly lower mortality than the late norepinephrine group (OR, 0.49; 95%, CI, 0.25-0.96). The early norepinephrine group demonstrated more mechanical ventilator-free days in observational studies (mean difference, 4.06; 95% CI, 2.82-5.30). The incidence of pulmonary edema was lower in the early norepinephrine group in the three RCTs that reported this outcome (OR, 0.43; 95% CI, 0.25-0.74). No differences were found in the other secondary outcomes.
CONCLUSIONS: Overall mortality did not differ significantly between early and late norepinephrine administration for septic shock. However, early norepinephrine administration seemed to reduce pulmonary edema incidence, and mortality improvement was observed in studies without fluid restriction interventions, favoring early norepinephrine use.

BACKGROUND: Surgery is often indicated in the treatment of medically recalcitrant chronic rhinosinusitis (CRS). There is conflicting evidence on the impact of timeliness of sinus surgery on the degree of perceived symptom improvement in CRS.
OBJECTIVE: The goal of this study was to systematically evaluate the available literature on the relationship between patient wait times for endoscopic sinus surgery (ESS) and postoperative changes in patient-reported outcome measures.
METHODS: Ovid, MEDLINE, CINAHL, and Cochrane Library of Systematic Reviews between January 2000 and September 1, 2023, were searched. A total of 931 studies were independently screened by 2 reviewers. Two studies were included in the meta-analysis, while 4 others were included in a narrative review.
RESULTS: Two studies consisting of 1606 patients were included in the meta-analysis. A mean difference in 22-Item Sino-Nasal Outcome Test (SNOT-22) of -0.3 (95% CI = -3.9 to 3.3, I2 = 89%, P < .01 was observed between \"long\" and \"short\" groups, while a mean difference in SNOT-22 of -0.1 (95% CI = -2.5 to 2.3, I2 = 80%, P = .03) was observed between \"long\" and \"mid\" groups. Patients who receive surgery earlier on their disease process (ie, earlier from the time of diagnosis to eventual surgery) appear to require less access to healthcare resources including prescription medications, thus suggesting better disease control.
CONCLUSIONS: There is conflicting evidence to conclude whether timing of ESS affects disease-specific measures in patients with CRS. Patients who receive surgery earlier appear to have lower demands on healthcare utilization including visits and prescription use. Our study suggests there is a need for increased access to surgical specialists who manage patients with CRS, and better understanding by primary care specialists in how to manage CRS when specialist access is not available.

BACKGROUND: Appendicectomy remains the standard treatment for appendicitis. There is a lack of clarity on the timeframe in which surgery should be performed to avoid unfavourable outcomes.
OBJECTIVE: To perform a systematic review and network meta-analysis to evaluate the impact the (1)time-of-day surgery is performed (2), time elapsed from symptom onset to hospital presentation (patient time) (3), time elapsed from hospital presentation to surgery (hospital time), and (4)time elapsed from symptom onset to surgery (total time) have on appendicectomy outcomes.
METHODS: A systematic review was performed as per PRISMA-NMA guidelines. The time-of-day which surgery was done was divided into day, evening and night. The other groups were divided into < 24 h, 24-48 h and > 48 h. The rate of complicated appendicitis, operative time, perforation, post-operative complications, surgical site infection (SSI), length of stay (LOS), readmission and mortality rates were analysed.
RESULTS: Sixteen studies were included with a total of 232,678 patients. The time of day at which surgery was performed had no impact on outcomes. The incidence of complicated appendicitis, post-operative complications and LOS were significantly better when the hospital time and total time were < 24 h. Readmission and mortality rates were significantly better when the hospital time was < 48 h. SSI, operative time, and the rate of perforation were comparable in all groups.
CONCLUSIONS: Appendicectomy within 24 h of hospital admission is associated with improved outcomes compared to patients having surgery 24-48 and > 48 h after admission. The time-of-day which surgery is performed does not impact outcomes.

Background: Postoperative physical therapy emerges as a pivotal element of the rehabilitation process, aimed at enhancing functional recovery, managing pain, and mitigating the risk of further complications. The debate concerning the optimal timing of physical therapy intervention post-surgery remains unresolved; in particular, whether to initiate physical therapy immediately or to wait weeks is of particular interest. The aim of this study is to review the available literature regarding the optimal timing of physical therapy initiation and the outcomes obtained. Methods: This review was carried out in accordance with the Preferential Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. This search was carried out in February 2024. Only peer-reviewed articles were considered for inclusion. Results: Fourteen studies were included. The primary outcomes assessed in the included studies were the following: 12-week and 12-month low back pain, return to work, function and disability, psychological status, patient satisfaction, and complications associated with early physical therapy. A meta-analysis was performed concerning low back pain after lumbar discectomy at 12 weeks and 12 months and complications after early physical therapy after lumbar discectomy and lumbar interbody fusion. A significant difference was found between early and standard physical therapy in terms of low back pain at 12-18 months (p = 0.0062); no significant differences were found in terms of complications, both for discectomy and arthrodesis. Conclusions: This review indicates that employing early rehabilitation strategies for intervertebral disc disease could enhance results in terms of pain and disability without an enhanced risk of complications.

UNASSIGNED: In patients with traumatic intracranial haemorrhage (tICH) there is significant risk of both venous thromboembolism (VTE) and haemorrhage progression. There is a paucity of literature to inform the timing of pharmacological thromboprophylaxis (PTP) initiation.
UNASSIGNED: This meta-analysis aims to summarise the current literature on the timing of PTP initiation in tICH.
UNASSIGNED: This meta-analysis followed the Methodological Expectations of Cochrane Intervention Reviews checklist and the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Following the literature search, studies were matched against the criteria for inclusion. Data from included studies was pooled, analysed using random-effect analysis and presented as forest plots of risk ratios, except one result reported as difference of means. The ROBINS-I tool was used to assess the risk of bias in the studies. The GRADE approach was taken to assess the quality of included studies. Heterogeneity of studies was assessed using Tau∧2. Funnel plots were generated and used in conjunction with Harbord\'s test and Rucker\'s arcsine to assess for small-study effect including publication bias.
UNASSIGNED: A total of 9927 ICH patients who received PTP were included from 15 retrospective observational cohort studies, 4807 patients received early PTP, the remaining 5120 received late PTP. The definition of early was dependent on the study but no more than 72-hours after admission. The mean age of the included cohort was 45.3 (std dev ±9.5) years, and the proportion of males was 71%. Meta-analysis indicated that there was a significant difference between early and late groups for the rate of VTE (RR, 0.544; p = 0.000), pulmonary embolus (RR, 0.538; p = 0.004), deep vein thrombosis (RR, 0.484; p = 0.000) and the intensive care unit length of stay (difference of means, -2.021; 95% CI, -2.250, -1.792; p = 0.000; Tau∧2 = 0.000), favouring the early group. However, the meta-analysis showed no significant difference between the groups for the rate of mortality (RR, 1.008; p = 0.936), tICH progression (RR, 0.853; p = 0.157), and neurosurgical intervention (RR, 0.870; p = 0.480).
UNASSIGNED: These findings indicated that early PTP appears to be safe and effective in patients with tICH.

Several recent studies have explored the relationships between mindfulness and time perception, an area of research that has become increasingly popular in the last 10-15 years. In this article, we present a systematic integrative review of the evidence on this subject. We also integrate the field\'s findings into a conceptual framework which considers the multifaceted nature of both mindfulness, and time perception research. To identify the relevant literature, we searched the following databases using relevant keywords: PsycINFO; Medline; EBSCO Host Psychology and Behavioral Sciences Collection; and Web of Science. These searches were last performed on the 4th of May 2022, and additional hand searches were also conducted. To be included, articles had to be in English and contain original data about the potential relationship(s) between mindfulness and time perception. Articles which did not present usable data about the relationship(s) between the variables of interest were excluded. In total, 47 research articles were included in the review (combined sample size of ∼5800 participants). Risks of bias in the selected studies were evaluated using two separate assessment tools designed for this purpose. Through an integrative narrative synthesis, this article reviews how mindfulness may relate to time perception for various reference frames, and for various time perception measures and methods. It also provides new insights by exploring how a wide range of findings can be integrated into a coherent whole, in light of some relevant time perception models and mindfulness theories. Altogether, the reviewed data suggest the existence of complex and multifaceted relationships between mindfulness and time perception, highlighting the importance of considering many factors when planning research or interpreting data in this field. Limitations of the current review include the scarceness of data for certain categories of findings, and the relatively low prevalence of studies with a randomized controlled design in the source literature. This research was partly funded by a grant from the Natural Science and Engineering Research Council of Canada.

Introduction: The World Health Organization (WHO) recommends vaccination against hepatitis B as soon as possible following birth for all infants, regardless of prematurity. Hepatitis B vaccination at birth is clearly justified, represents a crucial step in the global control of perinatally acquired hepatitis B and there are no safety concerns in infants born at term. However, there is limited information on the safety of the hepatitis B vaccine in preterm infants, whose immune responses and morbidity risk differ from those in infants born at term. Objectives: The objectives of this paper are to systematically review the literature regarding the safety and risk of adverse events following immunisation (AEFIs) associated with the administration of the hepatitis B vaccine (monovalent or as part of a combination vaccine) to preterm infants. Methods: We performed a search for relevant papers published between 1 January 2002 and 30 March 2023 in the Ovid MEDLINE, Ovid Embase, Cochrane Central Register of Controlled Trials and CINAHL Plus databases. Two authors independently reviewed and analysed each article to include in the systematic review. Narrative synthesis is presented. Results: Twenty-one relevant papers were identified and included in this systematic review. The vast majority of data pertained to multi-antigen (combination) vaccine preparations and vaccination episodes from 6 weeks of age onwards. We found no publications investigating the timing of the birth dose of the hepatitis B vaccine, and AEFI reporting was exclusively short-term (hours to days following administration). There was substantial variability in the reported rate of AEFIs between studies, ranging from 0% to 96%. Regardless of frequency, AEFIs were mostly minor and included injection site reactions, temperature instability and self-limiting cardiorespiratory events. Six studies reported serious adverse events (SAEs) such as the requirement for escalation of respiratory support. However, these occurred predominantly in high-risk infant populations and were rare (~1%). Using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach, the certainty of evidence was assessed as very low. Conclusions: Despite substantial variability between the relatively small number of published studies in terms of cohort selection, definitions, vaccine preparations and reporting, hepatitis B-containing vaccines (mostly as combination vaccines) appear to be relatively well tolerated in preterm infants from 6 weeks of age. Research focusing on the safety of hepatitis B vaccine in preterm infants specifically within 7 days of birth is lacking, particularly regarding long-term morbidity risk. Further research in this area is required.

Introduction  Meningiomas-the most common extra-axial tumors-are benign, slow-growing dural-based lesions that can involve multiple cranial fossae and can progress insidiously for years until coming to clinical attention secondary to compression of adjacent neurovascular structures. For complex, multicompartmental lesions, multistaged surgeries have been increasingly shown to enhance maximal safe resection while minimizing adverse sequela. Here, we systematically review the extant literature to highlight the merits of staged resection. Methods  PubMed, Scopus, and Web of Science databases were queried to identify articles reporting resections of intracranial meningiomas using a multistaged approach, and articles were screened for possible inclusion in a systematic process performed by two authors. Results  Of 118 identified studies, 36 describing 169 patients (mean age 42.6 ± 21.3 years) met inclusion/exclusion criteria. Petroclival lesions comprised 57% of cases, with the most common indications for a multistaged approach being large size, close approximation of critical neurovascular structures, minimization of brain retraction, identification and ligation of deep vessels feeding the tumor, and resection of residual tumor found on postoperative imaging. Most second-stage surgeries occurred within 3 months of the index surgery. Few complications were reported and multistaged resections appeared to be well tolerated overall. Conclusions  Current literature suggests multistaged approaches for meningioma resection are well-tolerated. However, there is insufficient comparative evidence to draw definitive conclusions about its advantages over an unstaged approach. There are similarly insufficient data to generate an evidence-based decision-making framework for when a staged approach should be employed. This highlights the need for collaborative efforts among skull base surgeons to establish an evidentiary to support the use of staged approaches and to outline those indications that merit such an approach.