Objectives: Orthostatic hypotension is a potential risk factor for falls in older adults, but existing evidence on this relationship is inconclusive. This study addresses the association between orthostatic hypotension and falls. Design: Systematic review and meta-analysis of the cross-sectional and longitudinal studies assessing the association between orthostatic hypotension and falls, as preregistered in the PROSPERO database (CRD42017060134). Setting and participants: A literature search was performed on February 20, 2017, in MEDLINE (from 1946, PubMed (from 1966), and EMBASE (from 1947) using the terms orthostatic hypotension, postural hypotension, and falls. References of included studies were screened for other eligible studies. Study selection was performed independently by 2 reviewers using the following inclusion criteria: published in English; mean/median age of the population !65 years; blood pressure measurement before and after postural change; and assessment of the association of orthostatic hypotension with falls. The following studies were excluded: conference abstracts, case reports, reviews, and editorials. Data extraction was performed independently by 2 reviewers. Measures: Unadjusted odds ratios of the association between orthostatic hypotension and falls were used for pooling using a random effects model. Studies were rated as high, moderate, or low quality using the Newcastle-Ottawa Scale. Results: Out of 5646 studies, 63 studies (51,800 individuals) were included in the systematic review and 50 studies (49,164 individuals) in the meta-analysis. Out of 63 studies, 39 were cross-sectional and 24 were longitudinal. Orthostatic hypotension was positively associated with falls (odds ratio 1.73, 95% confidence interval 1.50-1.99). The result was independent of study population, study design, study quality, orthostatic hypotension definition, and blood pressure measurement method. Conclusions and implications: Orthostatic hypotension is significantly positively associated with falls in older adults, underpinning the clinical relevance to test for an orthostatic blood pressure drop and highlighting the need to investigate orthostatic hypotension treatment to potentially reduce falls.
Background Neonatal early-onset sepsis (EOS) is one of the main causes of global neonatal mortality and morbidity, and initiation of early antibiotic treatment is key. However, antibiotics may be harmful. Methods We performed a secondary analysis of results from the Neonatal Procalcitonin Intervention Study, a prospective, multicenter, randomized, controlled intervention study. The primary outcome was the diagnostic accuracy of serial measurements of C-reactive protein (CRP), procalcitonin (PCT), and white blood count (WBC) within different time windows to rule out culture-positive EOS (proven sepsis). Results We analyzed 1678 neonates with 10 899 biomarker measurements (4654 CRP, 2047 PCT, and 4198 WBC) obtained within the first 48 hours after the start of antibiotic therapy due to suspected EOS. The areas under the curve (AUC) comparing no sepsis vs proven sepsis for maximum values of CRP, PCT, and WBC within 36 hours were 0.986, 0.921, and 0.360, respectively. The AUCs for CRP and PCT increased with extended time frames up to 36 hours, but there was no further difference between start to 36 hours vs start to 48 hours. Cutoff values at 16 mg/L for CRP and 2.8 ng/L for PCT provided a sensitivity of 100% for discriminating no sepsis vs proven sepsis. Conclusions Normal serial CRP and PCT measurements within 36 hours after the start of empiric antibiotic therapy can exclude the presence of neonatal EOS with a high probability. The negative predictive values of CRP and PCT do not increase after 36 hours.
BACKGROUNDWorldwide, many newborns who are preterm, small or large for gestational age, or born to mothers with diabetes are screened for hypoglycemia, with a goal of preventing brain injury. However, there is no consensus on a treatment threshold that is safe but also avoids overtreatment. METHODSIn a multicenter, randomized, noninferiority trial involving 689 otherwise healthy newborns born at 35 weeks of gestation or later and identified as being at risk for hypoglycemia, we compared two threshold values for treatment of asymptomatic moderate hypoglycemia. We sought to determine whether a management strategy that used a lower threshold (treatment administered at a glucose concentration of <36 mg per deciliter [2.0 mmol per liter]) would be noninferior to a traditional threshold (treatment at a glucose concentration of <47 mg per deciliter [2.6 mmol per liter]) with respect to psychomotor development at 18 months, assessed with the Bayley Scales of Infant and Toddler Development, third edition, Dutch version (Bayley-III-NL; scores range from 50 to 150 [mean {±SD}, 100±15]), with higher scores indicating more advanced development and 7.5 points (one half the SD) representing a clinically important difference). The lower threshold would be considered noninferior if scores were less than 7.5 points lower than scores in the traditional-threshold group. RESULTS Bayley-III-NL scores were assessed in 287 of the 348 children (82.5%) in the lower-threshold group and in 295 of the 341 children (86.5%) in the traditional-threshold group. Cognitive and motor outcome scores were similar in the two groups (mean scores [±SE], 102.9±0.7 [cognitive] and 104.6±0.7 [motor] in the lower-threshold group and 102.2±0.7 [cognitive] and 104. 9±0.7 [motor] in the traditional-threshold group). The prespecified inferiority limit was not crossed. The mean glucose concentration was 57±0.4 mg per deciliter (3.2±0.02 mmol per liter) in the lower-threshold group and 61±0.5 mg per deciliter (3.4±0.03 mmol per liter) in the traditional-threshold group. Fewer and less severe hypoglycemic episodes occurred in the traditional-threshold group, but that group had more invasive diagnostic and treatment interventions. Serious adverse events in the lower-threshold group included convulsions (during normoglycemia) in one newborn and one death. CONCLUSIONSIn otherwise healthy newborns with asymptomatic moderate hypoglycemia, a lower glucose treatment threshold (36 mg per deciliter) was noninferior to a traditional threshold (47 mg per deciliter) with regard to psychomotor development at 18 months. (Funded by the Netherlands Organization for Health Research and Development; HypoEXIT Current Controlled Trials number, ISRCTN79705768.
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