RECENT FINDINGS: A major care gap persists throughout the world in the secondary prevention of fragility fractures. Systematic reviews have confirmed that the Fracture Liaison Service (FLS) model of care is associated with significant improvements in rates of bone mineral density testing, initiation of osteoporosis treatment and adherence with treatment for individuals who sustain fragility fractures. Further, these improvements in the processes of care resulted in significant reductions in refracture risk and lower post-fracture mortality. The primary challenge facing health systems now is to ensure that best practice is delivered effectively in the local healthcare setting. Publication of clinical standards for FLS at the organisational and patient level in combination with the establishment of national registries has provided a mechanism for FLS to benchmark and improve their performance. Major efforts are ongoing at the global, regional and national level to improve the acute care, rehabilitation and secondary prevention for individuals who sustain fragility fractures. Active participation in these initiatives has the potential to eliminate current care gaps in the coming decade.
RESULTS: A total of 3412 (2001 annotated) gene candidates were found to be significantly differentially expressed between high- and low-yielding palms at at least one of the different stages of mesocarp development evaluated. Gene Ontologies (GO) enrichment analysis identified 28 significantly enriched GO terms, including regulation of transcription, fatty acid biosynthesis and metabolic processes. These differentially expressed genes comprise several transcription factors, such as, bHLH, Dof zinc finger proteins and MADS box proteins. Several genes involved in glycolysis, TCA, and fatty acid biosynthesis pathways were also found up-regulated in high-yielding oil palm, among them; pyruvate dehydrogenase E1 component Subunit Beta (PDH), ATP-citrate lyase, β- ketoacyl-ACP synthases I (KAS I), β- ketoacyl-ACP synthases III (KAS III) and ketoacyl-ACP reductase (KAR). Sucrose metabolism-related genes such as Invertase, Sucrose Synthase 2 and Sucrose Phosphatase 2 were found to be down-regulated in high-yielding oil palms, compared to the lower yield palms.
CONCLUSIONS: Our findings indicate that a higher carbon flux (channeled through down-regulation of the Sucrose Synthase 2 pathway) was being utilized by up-regulated genes involved in glycolysis, TCA and fatty acid biosynthesis leading to enhanced oil production in the high-yielding oil palm. These findings are an important stepping stone to understand the processes that lead to production of high-yielding oil palms and have implications for breeding to maximize oil production.
METHODS: The study was based on prospective observational data from the first 1,300 patients included in the International GBS Outcome Study. We described the treatment practice of GBS in general, and for (1) severe forms (unable to walk independently), (2) no recovery after initial treatment, (3) treatment-related fluctuations, (4) mild forms (able to walk independently), and (5) variant forms including Miller Fisher syndrome, taking patient characteristics and hospital type into account.
RESULTS: We excluded 88 (7%) patients because of missing data, protocol violation, or alternative diagnosis. Patients from Bangladesh (n = 189, 15%) were described separately because 83% were not treated. IV immunoglobulin (IVIg), plasma exchange (PE), or other immunotherapy was provided in 941 (92%) of the remaining 1,023 patients, including patients with severe GBS (724/743, 97%), mild GBS (126/168, 75%), Miller Fisher syndrome (53/70, 76%), and other variants (33/40, 83%). Of 235 (32%) patients who did not improve after their initial treatment, 82 (35%) received a second immune modulatory treatment. A treatment-related fluctuation was observed in 53 (5%) of 1,023 patients, of whom 36 (68%) were re-treated with IVIg or PE.
CONCLUSIONS: In current practice, patients with mild and variant forms of GBS, or with treatment-related fluctuations and treatment failures, are frequently treated, even in absence of trial data to support this choice. The variability in treatment practice can be explained in part by the lack of evidence and guidelines for effective treatment in these situations.
METHODS: Cross-sectional baseline evaluation of EVOLVE: an international, multicenter, non-interventional study investigating the safety of injectable glucose-lowering drugs in pregnant women with pre-existing type 1 (T1D) or type 2 diabetes (T2D). Data were collected at enrollment visit interviews before gestational week 16.
RESULTS: In total, 2383 women from 17 mainly European countries were enrolled in the study: 2122 with T1D and 261 with T2D; mean age was 31 and 33 years, and duration of diabetes was 15 and 6 years, respectively. For women with T1D or T2D, 63% and 75%, respectively, received basal and rapid-acting insulin, 36% and 3% rapid-acting insulin only, 0.7% and 14.0% basal insulin only, 0.2% and 5.4% premix insulin, 0.0% and 1.2% injectable glucagon-like peptide-1 receptor agonist treatment without insulin. In women with T1D or T2D, respectively, during early pregnancy, 59% and 62% had HbA1c <7.0% (53 mmol/mol); 16% and 36% reported not taking folic acid before or during early pregnancy. Overall, >40% of women had ≥1 chronic concomitant condition (predominantly thyroid disease or hypertension). Retinopathy was the most commonly reported diabetic complication. The most commonly reported previous pregnancy complication was miscarriage.
CONCLUSIONS: Baseline data from this large multinational population of women with pre-existing diabetes indicate that sub-optimal glycemic control, poor pregnancy planning, and chronic concomitant conditions were common in early pregnancy.
RESEARCH DESIGN AND METHODS: Multinational, prospective cohort study to assess the prevalence of newborns free from major congenital malformations or perinatal or neonatal death (primary end point) following treatment with insulin detemir (detemir) versus other basal insulins.
RESULTS: Of 1,457 women included, 727 received detemir and 730 received other basal insulins. The prevalence of newborns free from major congenital malformations or perinatal or neonatal death was similar between detemir (97.0%) and other basal insulins (95.5%) (crude risk difference 0.015 [95% CI -0.01, 0.04]; adjusted risk difference -0.003 [95% CI -0.03, 0.03]). The crude prevalence of one or more congenital malformations (major plus minor) was 9.4% vs. 12.6%, with a similar risk difference before (-0.032 [95% CI -0.064, 0.000]) and after (-0.036 [95% CI -0.081, 0.009]) adjustment for confounders. Crude data showed lower maternal HbA1c during the first trimester (6.5% vs. 6.7% [48 vs. 50 mmol/mol]; estimated mean difference -0.181 [95% CI -0.300, -0.062]) and the second trimester (6.1% vs. 6.3% [43 vs. 45 mmol/mol]; -0.139 [95% CI -0.232, -0.046]) and a lower prevalence of major hypoglycemia (6.0% vs. 9.0%; risk difference -0.030 [95% CI -0.058, -0.002]), preeclampsia (6.4% vs. 10.0%; -0.036 [95% CI -0.064, -0.007]), and stillbirth (0.4% vs. 1.8%; -0.013 [95% CI -0.024, -0.002]) with detemir compared with other basal insulins. However, differences were not significant postadjustment.
CONCLUSIONS: Insulin detemir was associated with a similar risk to other basal insulins of major congenital malformations, perinatal or neonatal death, hypoglycemia, preeclampsia, and stillbirth.
METHODS: Sleep clinic patients were 3,965 consecutive adults diagnosed with OSA by in-laboratory polysomnography from 2006 to 2010 at a tertiary hospital sleep clinic. Characteristics of these patients were compared with participants of five recent RCTs examining the effect of CPAP on adverse CV events in OSA. The percentage of patients with severe (apnea-hypopnea index, [AHI] ≥ 30 events/h) or any OSA (AHI ≥ 5 events/h) who met the eligibility criteria of each RCT was determined, and those criteria that excluded the most patients identified.
RESULTS: Compared to RCT participants, sleep clinic OSA patients were younger, sleepier, more likely to be female and less likely to have established CV disease. The percentage of patients with severe or any OSA who met the RCT eligibility criteria ranged from 1.2% to 20.9% and 0.8% to 21.9%, respectively. The eligibility criteria that excluded most patients were preexisting CV disease, symptoms of excessive sleepiness, nocturnal hypoxemia and co-morbidities.
CONCLUSIONS: A minority of sleep clinic patients diagnosed with OSA meet the eligibility criteria of RCTs of CPAP on adverse CV events in OSA. OSA populations in these RCTs differ considerably from typical sleep clinic OSA patients. This suggests that the findings of such OSA treatment-related RCTs are not generalizable to sleep clinic OSA patients.Randomized Intervention with Continuous Positive Airway Pressure in CAD and OSA (RICCADSA) trial, https://clinicaltrials.gov/ct2/show/NCT00519597, ClinicalTrials.gov number, NCT00519597.Usefulness of Nasal Continuous Positive Airway Pressure (CPAP) Treatment in Patients with a First Ever Stroke and Sleep Apnea Syndrome, https://clinicaltrials.gov/ct2/show/NCT00202501, ClinicalTrials.gov number, NCT00202501.Effect of Continuous Positive Airway Pressure (CPAP) on Hypertension and Cardiovascular Morbidity-Mortality in Patients with Sleep Apnea and no Daytime Sleepiness, https://clinicaltrials.gov/ct2/show/NCT00127348, ClinicalTrials.gov number, NCT00127348.Continuous Positive Airway Pressure (CPAP) in Patients with Acute Coronary Syndrome and Obstructive Sleep Apnea (OSA) (ISAACC), https://clinicaltrials.gov/ct2/show/NCT01335087, ClinicalTrials.gov number, NCT01335087.