Identification of Risk Factors for Gliptin-associated Bullous Pemphigoid among Diabetic Patients.

Drug-associated bullous pemphigoid has been shown to follow long-term gliptin (dipeptidyl-peptidase 4 inhibitors) intake. This study aimed at identifying risk factors for gliptin-associated bullous pemphigoid among patients with type 2 diabetes. A retrospective study was conducted in a tertiary centre among diabetic patients exposed to gliptins between the years 2008-2021. Data including demographics, comorbidities, medications, and laboratory results were collected using the MDClone platform. Seventy-six patients with type 2 diabetes treated with dipeptidyl-peptidase 4 inhibitors who subsequently developed bullous pemphigoid were compared with a cohort of 8,060 diabetic patients exposed to dipeptidyl-peptidase 4 inhibitors who did not develop bullous pemphigoid. Based on a multivariable analysis adjusted for age and other covariates, Alzheimer's disease and other dementias were significantly more prevalent in patients with bullous pemphigoid (p = 0.0013). Concomitant use of either thiazide or loop diuretics and gliptin therapy was associated with drug-associated bullous pemphigoid (p < 0.0001 for both). While compared with sitagliptin, exposure to linagliptin and vildagliptin were associated with bullous pemphigoid with an odds ratio of 5.68 and 6.61 (p < 0.0001 for both), respectively. These results suggest gliptins should be prescribed with caution to patients with type 2 diabetes with coexisting Alzheimer's and other dementias, or patients receiving long-term use of thiazides and loop diuretics. The use of sitagliptin over linagliptin and vildagliptin should be preferred in these patients.

Healthcare utilization is increased in children living in urban areas, with ethnicity-related disparities: A big data analysis study.

This study aimed to investigate differences in pediatric healthcare utilization in Israel over 10 years by examining differences across populations defined by living environment and ethnicity. Data was obtained from the Clalit Health Care data warehouse, covering over 250,000 children residing in Haifa and Western Galilee districts. The population groups were categorized based on ethnicity (Jewish vs Arab) and residential settings (urban vs rural). Healthcare utilization was consistently higher among Jewish than Arab children, irrespective of the specific dimension analyzed. Additionally, urban-dwelling children exhibited higher usage rates than those residing in rural areas in all investigated dimensions. However, Jewish children showed significantly about 18% lower hospitalization rates than Arab children across all years (P < 0.001). No significant differences in hospitalizations were observed between urban and rural children (RR 0.999, CI (0.987-1.011)). Notably, the study revealed reduced antibiotic consumption and hospitalizations over the years for all populations. Additionally, we found that Arab children and those living in rural areas had reduced access to healthcare, as evidenced by 10-40% fewer physician visits, laboratory tests, and imaging (P < 0.001).    Conclusion: This study highlights the substantial population-based disparities in healthcare utilization among children in Israel despite the equalizing effect of the national health insurance law. Rural and low socioeconomic populations seem to have reduced healthcare access, showing decreased healthcare utilization. Consequently, it is imperative to address these disparities and implement targeted interventions to enhance healthcare access for Arab children and rural communities. The decline in antibiotic usage and hospitalizations suggests positive trends in pediatric health care, necessitating ongoing efforts to ensure equitable access and quality of care for all populations. What is Known: • Healthcare systems worldwide vary in coverage and accessibility, including Israel, which stands out for its diverse population. • Existing research primarily focuses on healthcare utilization among adults, leaving a need for comprehensive data on children's healthcare patterns globally. What is New: • Investigating over 250,000 children, this study reveals higher healthcare utilization among Jewish and urban children across all dimensions. • Despite Israel's national health insurance law, the study underscores the significant population-based disparities in healthcare utilization.

Multisystemic inflammatory syndrome in children and the BNT162b2 vaccine: a nationwide cohort study.

Multisystemic inflammatory syndrome in children (MIS-C) is a rare, severe, post-infectious hyperinflammatory condition that occurs after COVID-19 infection. In this study, we aimed to demonstrate the risk reduction of MIS-C and severe MIS-C after Pfizer-BioNTech BNT162b2 mRNA COVID-19 vaccination. This nationwide cohort study included 526,685 PCR-confirmed COVID-19 cases (age < 19 years), of whom 14,118 were fully vaccinated prior to COVID-19 infection. MIS-C cases were collected from all hospitals in Israel from April 2020 through November 2021. The MIS-C rates were calculated among two COVID-19 populations: positive PCR confirmed cases and estimated COVID-19 cases (PCR confirmed and presumed). Vaccination status was determined from Ministry of Health (MoH) records. The MIS-C risk difference (RD) and 95% confidence intervals (95%CI) between vaccinated and unvaccinated patients are presented. Overall, 233 MIS-C cases under the age of 19 years were diagnosed and hospitalized in Israel during the study period. Among the estimated COVID-19 cases, MIS-C RD realistically ranged between 2.1 [95%CI 0.7-3.4] and 1.0 [95%CI 0.4-1.7] per 10,000 COVID-19 cases. For severe MIS-C, RD realistically ranged between 1.6 [95%CI 1.3-1.9] and 0.8 [95%CI 0.7-1.0], per 10,000 COVID-19 cases. Sensitivity analysis was performed on a wide range of presumed COVID-19 rates, demonstrating significant RD for each of these rates. CONCLUSION: This research demonstrates that vaccinating children and adolescents against COVID-19 has reduced the risk of MIS-C during the study period. WHAT IS KNOWN: • Most of the published literature regarding vaccine effectiveness is based on case-control studies, which are limited due to small sample sizes and the inability to fully estimate the risk of MIS-C among vaccinated and unvaccinated children and adolescents. • The known underestimation of COVID-19 diagnosis among children and adolescents is challenging, as they often have few to no symptoms. WHAT IS NEW: • Significant risk difference was found in favor of the vaccinated group, even after including extreme assumptions regarding the underdiagnosed COVID-19 rate. • During this nationwide study period, it was found that vaccinating children and adolescents reduced the risk of MIS-C and its complications.

Minimal Learning Curve for Minimally Invasive Aortic Valve Replacement.

BACKGROUND: Minimally invasive aortic valve replacement (MiAVR) is an established technique for surgical aortic valve replacement (AVR). Although MiAVR was first described in 1993 and has shown good results compared with full sternotomy AVR (FSAVR) only a minority of patients undergo MiAVR. We recently started using MiAVR via an upper hemisternotomy. We aimed to examine the early results of our initial experience with this technique. METHODS: We compared 55 MiAVR patients with a historical cohort of 142 isolated FSAVR patients (December 2016-December 2022). The primary outcome was in-hospital mortality. Secondary outcomes included cardiopulmonary bypass (CPB) and cross-clamp times, blood product intake, in-hospital morbidity, and length of intensive care unit and hospital stay. RESULTS: There was no significant difference in preoperative characteristics, including age, laboratory values, and comorbidities. There was no significant difference between the groups regarding in-hospital mortality (FSAVR 3.52 vs. MiAVR 1.82%). There was no significant difference in CPB time (FSAVR 103.5 [interquartile range: 82-119.5] vs. MiAVR 107 min [92.5-120]), aortic cross-clamp time (FSAVR 81 [66-92] vs. MiAVR 90 min [73-99]), and valve size (FSAVR 23 [21-25] vs. MiAVR 23 [21-25]). The incidence of intraoperative blood products transfusion was significantly lower in the MiAVR group (10.91%) compared with the FSAVR group (25.35%, p = 0.03). CONCLUSION: Our findings further establish the possibility of reducing invasiveness of AVR without compromising patient safety and clinical outcomes. This is true even in the learning curve period and without requiring any significant change in the operative technique and dedicated equipment.

Factors associated with home epinephrine-treated reactions during peanut and tree-nut oral immunotherapy.

BACKGROUND: Home reactions requiring epinephrine administration, a marker of their severity, restrict the widespread use of oral immunotherapy (OIT), but their risk factors are largely not known. OBJECTIVE: To identify risk factors for such reactions during OIT to most allergenic foods. METHODS: All patients who began OIT for peanut, tree nuts, sesame, or egg allergy at the Shamir Medical Center between April 2010 and January 2020 were enrolled. The patients were instructed to use their epinephrine autoinjectors during reactions consisting of severe abdominal pain, significant shortness of breath, or lethargy, or whenever in uncertainty of reaction severity. Patients with and without home epinephrine-treated reactions (HETRs) were compared. RESULTS: A total of 757 OIT treatments for peanut (n = 346), tree nuts (n = 221; walnut n = 147, cashew n = 57, hazelnut n = 16, almond n = 1), sesame (n = 115), and egg (n = 75) allergies were administered to 644 patients. Eighty-three (10.9%) patients experienced HETRs. The highest rate of HETRs was experienced during walnut (20.4%) or hazelnut (25%) OIT, followed by peanut (9.8%), sesame (6.1%), egg (6.7%), and cashew (5.3%) OIT. Risk factors for HETRs included a reaction treated in an emergency department (ER) (P = .005) before starting OIT and a reaction treated with epinephrine during in-clinic induction (P < .001). Significantly fewer patients with (73.6%) than without (88.3%) HETRs achieved full desensitization (P = .001), but only a few patients with HETRs (8.4%) failed treatment. CONCLUSION: Previous reaction severity is the main predictor for HETRs during OIT. These reactions are more frequent during walnut and hazelnut OIT than during OIT for other foods studied. Most patients experiencing HETRs achieved desensitization.

Implementation of a Short-term Treatment Protocol in Anemic Patients before Cardiac Surgery.

BACKGROUND: We assessed whether implementation of an immediate preoperative treatment in anemic patients could result in fewer perioperative packed red blood cell (PRBC) transfusions and improved outcomes in a real-world setting. METHODS: From January 1, 2020, to November 31, 2022, we implemented a perioperative protocol for anemic patients (hemoglobin (Hb) level in women <11.5 g/dL, men <12.5 g/dL), which included subcutaneous erythropoietin α, intravenous Iron, and intramuscular vitamin B12 (all given preoperatively) and per os iron and folic acid given once a day postoperatively. We retrospectively compared all patients receiving the protocol to all eligible patients who were operated upon in the 4 years prior to implementation of the protocol. Primary outcome was amount of PRBC transfusions during surgery and index admission. RESULTS: In the months after protocol implementation, 114 patients who received the treatment protocol were compared with 236 anemic patients in the 4 years prior to who did not receive the protocol. The treatment reduced total PRBC use (control group median 4 [2-7] units vs. treatment 2 [1-3] units, p < 0.0001) and the incidence of postoperative blood products transfusions (treatment group 58 patients, 50.88% vs. control group 177 patients, 75%, p < 0.0001). Hb prior to discharge was higher among the protocol group (treatment median 9 g/dL [8.3-9.5 g/dL] vs. control 8.6 g/dL [8.1-9.1 g/dL], p = 0.0081). CONCLUSION: Despite some differences compared with previously described protocols, the implementation of a perioperative treatment protocol for anemic patients was associated with a reduction in PRBC transfusion in a real-world setting.

Non-inferiority of metronidazole to vancomycin in the treatment of first episode non-severe Clostridioides difficile infection: a single center retrospective cohort study.

OBJECTIVES: We sought to assess the effectiveness of oral vancomycin compared to metronidazole on recurrence and mortality among hospitalized patients with non-severe Clostridioides difficile infection (CDI). METHODS: A single center retrospective cohort study was conducted, including adult patients hospitalized between 2015 and 2020 with a first episode of non-severe CDI, treated with metronidazole or vancomycin as monotherapy for at least 10 days. We assessed recurrence of CDI requiring hospitalization (primary outcome) and all-cause mortality up to 8 weeks, post discharge. RESULTS: Overall, 160 patients were treated with vancomycin and 149 treated with metronidazole. Re-hospitalization within 8 weeks due to CDI occurred in 10 (6.2%) patients in the vancomycin group, and 13 (8.7%) in the metronidazole group (P value = 0.407). Eight-week mortality occurred in 39 patients (26.2%) in the metronidazole group and 46 patients (28.8%) in the vancomycin group (P value = 0.61). After adjusting for age, gender, Ischemic heart disease, white blood cell count, neutrophile count and CRP, there was no significant difference between the two treatments (Re-hospitalization in 8 weeks due to CDI P = 0.5059; In-hospital death P = 0.7950; 4-week mortality P = 0.2988; 8-week mortality P = 0.8237). CONCLUSION: There is no benefit of using vancomycin compared to metronidazole concerning recurrence rate requiring hospitalization, in-hospital and up to 4- and 8-week mortality rate in non-severe first episode of CDI.

Tissue microarrey: a potential cost-effective approach for mismatch repair testing in colorectal cancer.

BACKGROUND: Deficiencies in Mismatch Repair (MMR) proteins are one of the major pathways in the development of colorectal cancer (CRC). MMR status evaluation is recommended in every new CRC patient. However, this is not fully implemented due to high costs. Tissue microarray (TMA) enables allocating tissue cores from few specimens to a single paraffin block. The primary objective of this study was to evaluate the accuracy of TMA MMR immunohistochemistry (IHC) compared to whole slide. The secondary objective was to evaluate and validate automatic digital image analysis software in differentiating pathological and normal TMA cores. METHODS: Pathological cores were defined if at least one MMR protein was unstained. Tumoral and normal tissue of 11 CRC patients with known MMR status was used to obtain 623 TMA cores. The MMR staining of each core was evaluated by a pathologist and compared to the whole slide result. Digital analysis software by 3DHistech Ltd. was used to identify cell nucleus and quantify nuclear staining in 323 tissue cores. To identifying pathological tissue, cores the cohort was divided into a test (N = 146 cores) and validation sets (N = 177 cores). A staining intensity score (SIS) was developed, and its performance compared to the pathologist review of each core and to the whole slide result. RESULTS: Compared to the whole slide, the pathologist's assessment had 100% sensitivity (n/N = 112/112) and 100% specificity (n/N = 278/278) with 95% lower limit of 97 and 99% respectively. The area under the receiver operating characteristic (ROC) curve of SIS was 77%. A cutoff of 55 was obtained from the ROC curve. By implementing the cutoff in the validation dataset, the SIS had sensitivity and specificity of 98.2% [90.1-100%] and 58.5% [49.3-67.4%] respectively. CONCLUSIONS: The MMR status of CRC can be evaluated in TMA tissue cores thus potentially reducing MMR testing costs. The SIS can be used as triage indicator during pathologic review. TRIAL REGISTRATION: Institutional ethical approval was granted for the performance of this study (Emek Medical Center Ethics ID: EMC-19-0179).

Gender differences in measles incidence rates in a multi-year, pooled analysis, based on national data from seven high income countries.

BACKGROUND: Gender differences in a number of infectious diseases have been reported. The evidence for gender differences in clinical measles incidence rates has been variable and poorly documented over age groups, countries and time periods. METHODS: We obtained data on cases of measles by sex and age group over a period of 11-27 years from seven countries. Male to female incidence rate ratios (IRR) were computed for each year, by country and age group. For each age group, we used meta-analytic methods to combine the IRRs. Meta-regression was conducted to the estimate the effects of age, country, and time period on the IRR. RESULTS: In the age groups < 1, 1-4, 5-9, 10-14, 15-44, and 45-64 the pooled IRRs (with 95% CI) were 1.07 (1.02-1.11), 1.10 (1.07-1.14), 1.03 (1.00-1.05), 1.05 (0.99-1.11), 1.08 (0.95-1.23), and 0.82 (0.74-0.92) respectively. The excess incidence rates (IR) from measles in males up to age 45 are remarkably consistent across countries and time-periods. In the age group 45-64, there is an excess incidence in women. CONCLUSIONS: The consistency of the excess incidence rates in young males suggest that the sex differences are more likely due to physiological and biological differences and not behavioral factors. At older ages, differential exposure can play a part. These findings can provide further keys to the understanding of mechanisms of infection and tailoring vaccination schedules.

Medical clown support is associated with better quality of life of children with food allergy starting oral immunotherapy.

BACKGROUND: The start of oral immunotherapy (OIT) for food allergy is a critical period in the treatment process, with a potential to influence patient quality of life (QOL) and subsequently treatment outcome. The association of medical clowning with QOL at OIT initiation was examined. METHODS: Children aged 4-12 years supported by a medical clown (MC) during the induction week of OIT for food allergy were studied. Children in the same age range starting OIT without the support of a MC served as controls. Parents of all children completed the Food Allergy Quality of Life Questionnaire-Parent Form (FAQLQ-PF), and children aged 8-12 years completed the Food Allergy Quality of Life Questionnaire-Child Form (FAQLQ-CF). QOL scores of parents and children with and without a MC support were compared. RESULTS: Children with (n = 88) and without (n = 212) the support of a MC were comparable in demographics and clinical characteristics. The study group had a significantly lower single highest tolerated dose compared to controls (57 ± 83 vs 162 ± 274 mg protein, respectively, P < .001). Parental perception of the QOL of children was not associated with a MC support (P = .81) but rather with previous reaction severity (P < .01). In contrast, the QOL of children aged 8-12 years (n = 119) was positively associated primarily with a MC support, total score 3.7 ± 1.1 vs 4.6 ± 1.3 (P < .001). CONCLUSIONS: While the perception of QOL of parents of children with food allergy at OIT initiation is mainly associated with previous reaction severity, the QOL of the children themselves is primarily positively associated with MC support.

Effects of Recommendations for Diabetes Management at Hospital Discharge on Long-Term Diabetes Control.

OBJECTIVE: To determine the impact of diabetes-specific recommendations at 1 year after hospital discharge on glycemic control and diabetes care in an outpatient setting. METHODS: A total of 139 patients with type 2 diabetes on a basal-bolus insulin regimen during hospitalization were included in the statistical analysis. We gathered data on treatment regimens after 12 to 16, 26 to 30, and 52 to 56 weeks following discharge as well as glycosylated hemoglobin (HbA1c) levels for all patients. Prescriptions for diabetes therapy were retrieved. All changes in insulin or oral/noninsulin injectable drug regimens were recorded. RESULTS: Half of the patients (n = 69) were discharged on their preadmission regimen (no change), and a change in the home treatment was recommended in the other half (n = 70). In the group of patients whose preadmission therapy was adjusted, HbA1c decreased from 9.6% (80 mmol/mol) to 8.5% (69 mmol/mol) (P = .0004) 1 year after discharge. In the group of patients discharged on their preadmission regimen, no significant changes in HbA1c levels during the study were observed. At follow-ups occurring 12 to 16 weeks after discharge, 52% (95% CI: 37.4%-66.3%) of patients in the change group had their treatment modified, compared with 18.6% (95% CI: 9.7%-30.9%) in the no-change group. In the group of patients discharged on their preadmission regimen, no significant change was observed. At the beginning of the study, patients in the change treatment group had higher HbA1c levels than patients in the no-change group (9.6 ± 2.0 vs 8.6 ± 1.7, P < .001). At the end of the study, no significant changes in terms of HbA1c levels were found between the groups (8.8 ± 1.9 vs 8.5 ± 1.9, P = .2). CONCLUSIONS: Significant improvement in diabetes control occurred 1 year after hospital discharge in patients who underwent modifications in their treatment. This supports the relevance of providing and implementing proper care recommendations at transition.

One elevated oral glucose tolerance test value in pregnancy increases the risk for future diabetes mellitus type 2.

PURPOSE: Women with only one elevated 100 g OGTT value are not considered as having gestational diabetes mellitus (GDM) and therefore there are no recommendations to address this population as a risk group for type 2 diabetes mellitus (T2DM). We aimed to elucidate whether one elevated OGTT value increases the risk for T2DM. METHODS: A retrospective population-based cohort study of women with a first diagnosis of GDM who delivered between 1991 and 2011 was conducted. Women were divided according to GDM diagnosis criteria into three groups: (1) at least two elevated values of Carpenter and Coustan criteria (C&C; N = 209), (2) At least two elevated values of the National Diabetes Data Group (NDDG) criteria (NDDG2; N = 290) and (3) only one elevated value of the NDDG criteria (NDDG1; N = 226). A fourth group comprising women without GDM was included (control; N = 352). The primary outcome was the development of T2DM. RESULTS: The mean follow-up was 12.4 ± 5.3 years and the mean age at follow-up was 43.0 ± 5.7 years. The rate of T2DM in the control, C&C, NDDG1 and NDDG2 groups were 5%, 18%, 19% and 31%, respectively. All GDM diagnoses were independent risk factors for T2DM in multivariable Cox regression when compared to controls, adjusted hazard ratio and 95% CI: C&C 7.8 [95% CI 3.7-16.4], NDDG1 5.5 [2.6-11.6], and NDDG2 10.5 [5.2-21.4]. Additional independent risk factors were parity, fasting and 1-h post-glucose load of the OGTT and insulin use. CONCLUSIONS: Women with one elevated OGTT value using the NDDG criteria are at increased risk for T2DM. Further studies are needed to decide whether those women should be considered a focus group for long-term surveillance and T2DM prevention interventions.

A meta-analytic evaluation of sex differences in meningococcal disease incidence rates in 10 countries.

The magnitude and consistency of the sex differences in meningococcal disease incidence rates (IR) have not been systematically examined in different age groups, countries and time periods. We obtained national data on meningococcal disease IR by sex, age group and time period, from 10 countries. We used meta-analytic methods to combine the male to female incidence rate ratios (IRRs) by country and year for each age group. Meta-regression analysis was used to assess the contribution of age, country and time period to the variation in the IRRs. The pooled male to female IRRs (with 95% CI) for ages 0-1, 1-4, 5-9, 10-14 and 15-44, were 1.25 (1.19-1.32), 1.24 (1.20-1.29), 1.13 (1.07-1.20), 1.21 (1.13-1.29) and 1.15 (1.10-1.21), respectively. In the age groups 45-64 and over 65, the IR were lower in males with IRRs of 0.83 (0.78-0.88) and 0.64 (0.60-0.69), respectively. Sensitivity analysis and meta-regression confirmed that the results were robust. The excess meningococcal IR in young males and the higher rates in females at older ages were consistent in all countries, except the Czech Republic. While behavioural factors could explain some of the sex differences in the older age groups, the excess rates in very young males suggest that genetic and hormonal differences could be important.

Sex differences in campylobacteriosis incidence rates at different ages - a seven country, multi-year, meta-analysis. A potential mechanism for the infection.

BACKGROUND: There is evidence that males have higher incidence rates (IR) of campylobacteriois than females. The objectives of this study were to determine whether these observations differ between age groups and are consistent over different countries and during different time periods. METHODS: We obtained data on IRs of campylobacteriosis by sex and age group over a period of 11-26 years from seven countries. Male to female incidence rate ratios (IRR) were computed by age group, country and time period. For each age group, we used meta-analytic methods to combine the IRRs. Sensitivity analysis was used to test whether the results are robust to differences between countries and time periods. Meta-regression was conducted to estimate the different effects of age, country, and time period on the IRR. RESULTS: In the age groups < 1, 1-4, 5-9, 10-14, 15-44, 45-64 and 65+ years old, the pooled IRRs (with 95% CI) were 1.31 (1.26-1.37), 1.34 (1.31-1.37), 1.35 (1.32-1.38), 1.73 (1.68-1.79), 1.10 (1.08-1.12), 1.19(1.17-1.21) and 1.27 (1.24-1.30), respectively. For each age group, the excess campylobacteriosis IRs in males differed at different age groups. However, despite some quantitative differences between countries, the excess was consistently present over long time-periods. In meta-regression analysis, age group was responsible for almost all the variation in the IRRs. CONCLUSIONS: The male predominance in campylobacteriosis IRs starts in infancy. This suggests that this is due, at least in part, to physiological or genetic differences and not just behavioural factors. These findings can provide clues to the mechanisms of the infection and could lead to more targeted treatments and vaccine development.

Sex differences in shigellosis incidence rates: analysis of national data from nine countries using meta-analytic method.

BACKGROUND: Sex differences in the incidence of infectious diseases can provide insight to the biological mechanism of infection, disease susceptibility, severity and vaccine development. The consistency of age-specific sex differences in the incidence rates (IRs) of shigellosis is unclear. METHODS: National data on cases of shigellosis by sex, age group and calendar year were obtained from nine countries, for a period of 6-25 years. The male to female incidence rate ratios (RR) were calculated by country, years and age group. For each age group, meta-analytic methods were used for computing pooled incidence RRs by country and years. Meta-regression was performed to estimate the contribution of age, country and time period to the differences in the male : female RRs. RESULTS: In the age groups <1, 1-4, 5-9 and 10-14, there were excess IRs in males. The pooled incidence RRs (with 95% CI) were 1.21 (1.14-1.28), 1.17 (1.12-1.22), 1.04 (1.00-1.09) and 1.09 (1.01-1.18), respectively. In young adults, there was excess IR in females with RR = 0.80 (0.72-0.9). In middle aged and older adults, there was a slight excess in males with RR = 1.01 (0.89-1.15) and RR = 1.18 (1.09-1.28), respectively. In the meta-regression, age was the only variable that significantly contributed to the variation in the RRs. CONCLUSIONS: The higher IRs in male infants and young children does not appear to be related to behavioral factors and genetic and hormonal factors could be important. In the older age groups, the higher rates in adult females may be due to behavioral factors.

Intravenous iron treatment reduces coagulability in patients with iron deficiency anaemia: a longitudinal study.

Although many case reports and observational studies have reported a correlation between iron deficiency anaemia (IDA) and thrombotic events, the mechanism for this is poorly understood. To evaluate this, we examined the change in coagulability in patients receiving treatment for IDA. Adult patients with IDA were recruited for this study and treated with intravenous iron. The change in coagulability was assessed by thrombin generation using the calibrated automated thrombogram method. The change in factor VIII (FVIII) activity was later examined as a possible link. Forty-eight participants received intravenous iron and were included in this study. After treatment with intravenous iron, endogenous thrombin potential and peak height decreased in IDA patients by a mean of 122·4 nmol/l/min (95% confidence interval [CI]: 17·9-227, P = 0·023) and 51·9 (95% CI: 26·6-77·2, P < 0·001) respectively. Time to peak (peak time) increased by a mean of 23·6 s (95% CI: 5·4-41·9, P = 0·012). FVIII activity was reduced by a mean of 9·6% (95% CI: 2·54-16·7, P = 0·009). In conclusion, treating IDA reduces the blood's coagulability, as evidenced by the change in thrombin generation and FVIII activity levels. No correlation was found between the degree of iron deficiency correction and thrombogram parameters.

Good glycemic control of gestational diabetes mellitus is associated with the attenuation of future maternal cardiovascular risk: a retrospective cohort study.

BACKGROUND: To examine whether glycemic control of gestational diabetes mellitus (GDM) could modify the risk for future maternal metabolic and cardiovascular morbidities. METHODS: A retrospective cohort study of women with a first diagnosis of GDM who delivered between 1991 and 2011. Women were divided into groups of good and poor glycemic control, defined as a mean daily glucose of up to 95 mg/dL (N = 230) and more than 95 mg/dL (N = 216), respectively. In addition, a control group of women without GDM (N = 352) was also analyzed. The primary outcomes were the development of type 2 diabetes mellitus (T2DM), obesity, hypertension, or dyslipidemia. RESULTS: Mean follow-up time was 15.8 ± 5.1 years. Assessment was performed at a maternal age of 45 ± 7 years. The rates of the study outcomes in the control, GDM with good glycemic control and GDM with poor glycemic control were as follows: T2DM [19 (5.4%), 87 (38%), 127 (57%)]; hypertension [44 (13%), 42 (18%), 44 (20%)]; obesity [111 (32%), 112 (48%), 129 (58%)]; and dyslipidemia [49 (14%), 67 (29%), 106 (48%)]. Glycemic control was an independent risk factor for T2DM in multivariate Cox regression analysis (hazard ratio (HR) for poor glycemic control vs. controls 10.7 95% CI [6.0-19.0], good glycemic control vs. control HR 6.0 [3.3-10.8], and poor glycemic control vs. good glycemic control HR 1.8 [1.3-2.4]). Glycemic control was also an independent risk factor for dyslipidemia (poor glycemic control vs. controls HR 3.7 [2.3-5.8], good glycemic control vs. controls HR 2.0 [1.2-3.2], and poor glycemic control vs. good glycemic control HR 1.8 1.8 [1.3-2.6]). The fasting glucose level during oral glucose tolerance test (OGTT) was also an independent risk factor for these complications. The interaction term between glycemic control and the fasting value of the OGTT was not statistically significant, suggesting that the effect of glycemic control on the rate of future T2DM and dyslipidemia was not modified by the baseline severity of GDM. CONCLUSION: GDM and especially poor glycemic control are associated with T2DM and dyslipidemia. Strict glycemic control for reducing that risk should be evaluated in prospective trials.

Calibrated Automated Thrombogram During Pregnancy in Unexplained Recurrent Miscarriages: A Pilot Study.

BACKGROUND: Recurrent miscarriages are associated with a high prevalence of thrombophilia. Use of a calibrated automated thrombogram (CAT) can serve as a universal test for thrombophilia. OBJECTIVES: To examine whether thrombin generation measured by CAT is elevated during the first trimester in women with unexplained recurrent miscarriages. METHODS: This study comprised 25 pregnant women with recurrent pregnancy loss referred for thrombophilia screening and treated with low-molecular-weight heparin (LMWH). Thrombin generation parameters were measured in women who had miscarriages or live births and who were diagnosed as positive or negative for thrombophilia. RESULTS: Of the pregnancies, 76% resulted in live birth and 24% ended in miscarriages. Among the women, 76% were positive for thrombophilia. Thrombin generation parameters between pregnancies that ended in miscarriage compared to live births were not significantly different, and CAT parameters failed to predict pregnancy outcome. Although the CAT parameters demonstrated a trend toward a hypercoagulable state in women with thrombophilia, there was no statistical significance (P > 0.05). CONCLUSIONS: Women with unexplained pregnancy loss demonstrated similar thrombin generation in the first trimester, regardless of the pregnancy outcome. CAT parameters failed to predict pregnancy outcome in women with recurrent unexplained pregnancy loss. Our results should be interpreted with caution due to the small number of participants.

Glycemic control with a basal-bolus insulin protocol in hospitalized diabetic patients treated with glucocorticoids: a retrospective cohort study.

BACKGROUND: Improved glycemic control is the desired outcome after the discharge of patients with diabetes. We aimed to determine the efficacy of a basal-bolus insulin protocol in hospitalized patients with diabetes treated with glucocorticoids. METHODS: A retrospective cohort study compared the glycemic control of 150 hospitalized patients with diabetes and elevated inflammatory markers who were either treated with (n = 61) or without glucocorticoids (n = 89). All patients were treated with a basal-bolus regimen. RESULTS: Glycosylated hemoglobin A1C (HbA1C) levels, mode of diabetes treatment before admission, length of hospitalization and inflammatory markers were similar in both groups of patients (treated and untreated with glucocorticoid). There was a trend toward female predominance in the glucocorticoid-treated group. Mean daily glucose levels were higher in patients taking glucocorticoids when compared with untreated patients (12.5 ± 2.7 mmol/l vs. 10.9 ± 2.4 mmol/l, p < .0001), and significantly higher at 5:00 PM (13.1 ± 3.4 vs. 10.2 ± 3 mmol/l, p < .0001), and 8:00 P.M. (13.9 ± 4.1 mmol/l vs. 11 ± 3.1 mmol/l, p < 0.001) . No difference was detected between the two groups in prandial and basal insulin doses during hospitalization. Overall, 64% of patients in the glucocorticoid-treated group versus 39% in the untreated group had inadequate glycemic control during hospitalization (p = 0.003). CONCLUSION: A significantly higher percentage of patients with diabetes who were treated with glucocorticoids during hospitalization did not achieve glycemic control with a basal-bolus insulin protocol. These patients had significantly higher mean blood glucose levels due to elevated levels in the afternoon and evening. New basal-bolus protocols with appropriate adjustments of short acting insulin are needed to treat patients with diabetes on glucocorticoid therapy.

Labor induction versus expectant management at early term in pregnancies with second trimester elevated human chorionic gonadotropin or alpha fetoprotein.

AIM: Elevated human chorionic gonadotropin (HCG) and alpha fetoprotein (AFP) have been linked to placental dysfunction and associated morbidities. We aimed to compare the induction of labor with expectant management at term in those pregnancies for the prevention of neonatal and maternal morbidities. METHODS: Women with second trimester HCG ≥ 2 and/or AFP ≥ 2 multiples of the median, without additional maternal or fetal complications, from their 38th gestational week were offered the choice of labor induction or expectant management. The primary outcomes were maternal composite outcome (composed of cesarean deliveries, pre-eclampsia or placental abruption) and neonatal composite outcome (composed of antenatal or neonatal death, Apgar score at 5 min < 7, admission to the neonatal intensive care unit, need for phototherapy, respiratory abnormalities, birth trauma or neonatal infection). RESULTS: Of 305 women, 124 women chose to undergo labor induction, and 181 women chose expectant management. The composite maternal outcome in the expectant management group was twice the rate of the labor induction group, although it did not reach statistical significance (18 [10%] vs 6 [5%]; P = 0.1; relative risk [expectant/induced] 2.04; 95% confidence interval 0.8-5.0). Increased rate of phototherapy led to increased neonatal composite outcomes in the labor induction group compared with the expectant management group (34 [27%] vs 27 [15%], respectively = 0.007). CONCLUSION: In pregnancies with elevated AFP and/or HCG, early term labor induction initiated a trend towards improvement in maternal outcome but increased the rate of mild neonatal morbidity. The statistical insignificance of the large effect on the maternal outcome might reflect the lack of statistical power. Further research is needed to address this limitation.