Nonpregnant Adult Research Articles

Population PK modeling of certolizumab pegol in pregnant women with chronic inflammatory diseases.

Certolizumab pegol (CZP; CIMZIA™) is the only Fc-free tumor necrosis factor inhibitor with data from a clinical study demonstrating no to minimal placental transfer. The pharmacokinetics (PK) of certolizumab pegol during pregnancy and postpartum in women with chronic inflammatory diseases were assessed using a population PK model based on data from the CHERISH study (NCT04163016), a longitudinal, prospective, open-label PK phase IB study. Model development was performed in NONMEM using a frequentist prior approach, with prior information based on a population PK model for certolizumab pegol in non-pregnant adult patients (NCT04740814). A one-compartment model with first-order absorption (Ka = 0.236 1/day) and linear elimination (CL/F = 0.416 L/day) from the central compartment (V/F = 7.86 L) best described certolizumab pegol PK in the CHERISH study. The structural model parameters were estimated with good precision (RSE < 25%). Baseline BW was included as a covariate on CL/F and V/F. Pregnancy trimester and time-varying log-transformed anti-drug antibody (ADA) titer were identified as the only significant covariates for CL/F with a comparable influence on CL/F. Individuals with higher ADA titer (75th percentile) during pregnancy exhibited CL/F up to 1.43-fold higher relative to individuals postpartum that showed median levels of ADA titer. However, the confidence interval for the combined effect of pregnancy stage and ADA titer effects on CL/F overlapped with the CL/F range of the typical individual postpartum. In addition, simulations showed a large overlap in certolizumab pegol concentrations between pregnant and non-pregnant adults. The findings of this population PK analysis support the maintenance of established certolizumab pegol dosing regimens throughout pregnancy.

Altered angiogenic and neuroinflammatory markers in peripartum individuals with and without severe preeclampsia compared to non-pregnant adults (P3-5.008)

<h3>Objective:</h3> To characterize angiogenic and neuroinflammatory cytokine levels in serum and cerebrospinal fluid (CSF) of peripartum individuals with and without preeclampsia. <h3>Background:</h3> Preeclampsia, a hypertensive disorder of pregnancy associated with systemic endothelial dysfunction, carries high risk of neurovascular complications. Preliminary studies suggest maternal blood-brain barrier (BBB) dysfunction in preeclampsia. <h3>Design/Methods:</h3> We analyzed serum from 26 peripartum participants (13 severe preeclampsia, 13 normotensive controls), of whom 13 participants (7 cases, 6 controls) also had CSF available for analysis. ProcartaPlex and ELISA immunoassays were used to quantify angiogenic and neuroinflammatory proteins implicated in BBB dysfunction in serum and separately CSF. We used t-test or Wilcoxon tests to compare levels between participants with and without preeclampsia. We next compared our values to published normative values for healthy non-pregnant adults. We did not correct for multiple comparisons for this exploratory analysis. <h3>Results:</h3> We found no statistically significant difference in serum or CSF levels of angiogenic (VEGF, PlGF, and sFLT1) or neuroinflammatory (CCL5/RANTES, GM-CSF, CXCL10) markers between normotensive peripartum controls and those with severe preeclampsia. Compared to historical non-pregnant controls, serum levels in both cases and controls were lower of VEGF (p&lt;0.005 for both comparisons), CCL5 (p&lt;0.002 for both comparisons), and CXCL10 (p&lt;0.0.002 for both comparisons), and sFLT1 and GM-CSF were higher (p&lt;0.02 for all comparisons). In CSF analyses, the concentration of CXCL10 was significantly lower (p&lt;0.002 for both comparisons) and sFLT1 was significantly higher (p&lt;0.03 for both comparisons), compared with non-pregnant adult reference values. <h3>Conclusions:</h3> In this pilot study, angiogenic and neuroinflammatory profiles in the serum and CSF of peripartum individuals with and without severe preeclampsia were not significantly different. However, when compared with normative values for healthy non-pregnant adults, peripartum individuals demonstrate alterations in factors regulating BBB permeability. Our results suggest that the peripartum state may be associated with changes in BBB regulation, regardless of preeclampsia diagnosis. <b>Disclosure:</b> Miss Haghighi has nothing to disclose. Ms. Tuohy has nothing to disclose. Natalie Bello has nothing to disclose. Dr. Booker has nothing to disclose. Dr. Miltiades has nothing to disclose. Ronald Wapner has nothing to disclose. The institution of Dr. Marshall has received research support from NIH. Dr. Marshall has received publishing royalties from a publication relating to health care. Dr. Miller has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. Dr. Miller has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Argionis and Associates LLC. The institution of Dr. Miller has received research support from National Institutes of Health.

Serotype Distribution and Antimicrobial Resistance of Streptococcus agalactiae Isolates in Nonpregnant Adults with Streptococcal Toxic Shock Syndrome in Japan in 2014 to 2021.

The incidence of streptococcal toxic shock syndrome (STSS) due to group B Streptococcus (GBS) has been increasing annually in Japan and is becoming a serious challenge. Furthermore, in recent years, penicillin- or clindamycin-resistant strains used in treating streptococcal toxic shock syndrome have been reported. However, no report analyzed >100 isolates of group B Streptococcus causing streptococcal toxic shock syndrome. Therefore, we aimed to perform serotyping and antimicrobial susceptibility testing of 268 isolated group B Streptococcus strains from streptococcal toxic shock syndrome cases involving nonpregnant adult patients in Japan between 2014 and 2021. The most prevalent serotype was Ib, followed by serotypes V, III, and Ia. Seven isolates were resistant to penicillin G, and 17.9% (48 isolates) were resistant to clindamycin. Of the penicillin-resistant group B Streptococcus isolates, 71.4% (5 isolates) were clindamycin resistant. In addition, group B Streptococcus strains resistant to penicillin and clindamycin were isolated from patients with streptococcal toxic shock syndrome. Therefore, before these strains become prevalent, introduction of the group B Streptococcus vaccine is essential for disease prevention. IMPORTANCE Group B Streptococcus (GBS) has been increasingly associated with invasive disease in nonpregnant adults. Such infections are responsible for substantial morbidity and mortality, particularly in individuals with underlying chronic conditions. Streptococcal toxic shock syndrome (STSS) is a severe invasive infection characterized by the sudden onset of shock, multiorgan failure, and high mortality. In this study, we assessed 268 GBS-related STSS cases in nonpregnant adults in Japan between 2014 and 2021. Serotype Ib was the most prevalent, followed by serotypes V, III, and Ia, which were identified in more than 80% of STSS isolates. We found that 48 clindamycin-resistant strains and 7 penicillin G-resistant strains were isolated between 2014 and 2021. We believe that our study makes a significant contribution to the literature because we show that the GBS vaccine, particularly the hexavalent conjugate vaccine, is important to reduce the number of patients with STSS.

Burden of invasive group B Streptococcus disease in non-pregnant adults: A systematic review and meta-analysis.

Streptococcus agalactiae or group B Streptococcus (GBS) has emerged as an important cause of invasive disease in adults, particularly among the elderly and those with underlying comorbidities. Traditionally, it was recognised as an opportunistic pathogen colonising and causing disease in pregnant women, neonates, and young infants. Reasons for the upsurge of invasive GBS (iGBS) among the elderly remain unclear, although it has been related to risk factors such as underlying chronic diseases, immunosenescence, impaired inflammatory response, and spread of virulent clones. Antibiotics are successfully as treatment or prophylaxis against iGBS. Several candidate vaccines against iGBS are under development. To conduct a systematic review of the current literature on invasive GBS in order to determine disease incidence and case fatality ratio (CFR) among non-pregnant adults. Additionally, information on risk factors, clinical presentation, serotype distribution, and antimicrobial resistance was also retrieved. Between January and June 2020, electronic searches were conducted in relevant databases: MEDLINE, EMBASE, Global Health, and SCOPUS. Studies were included in the systematic review if they met the inclusion/exclusion criteria. The authors assessed the selected studies for relevance, risk of bias, outcome measures, and heterogeneity. Meta-analyses on incidence and CFR were conducted after evaluating the quality of methods for assessment of exposure and outcomes. Pooled estimates of iGBS incidence in non-pregnant adults 15 years and older were 2.86 cases per 100.000 population (95% CI, 1.68-4.34). Incidence rates in older adults were substantially higher, 9.13 (95%CI, 3.53-17.22) and 19.40 (95%CI, 16.26-22.81) per 100.000 population ≥50 and ≥ 65 years old, respectively. Incidence rates ranged from 0.40 (95% CI, 0.30-0.60) in Africa to 5.90 cases per 100.000 population (95% CI, 4.30-7.70) in North America. The overall CFR was and 9.98% (95% CI, 8.47-11.58). CFR was highest in Africa at 22.09% (95% CI, 12.31-33.57). Serotype V was the most prevalent serotype globally and in North America accounting for 43.48% (n = 12926) and 46,72% (n = 12184) of cases, respectively. Serotype Ia was the second and serotype III was more prevalent in Europe (25.0%) and Asia (29.5%). Comorbidities were frequent among non-pregnant adult iGBS cases. Antimicrobial resistance against different antibiotics (i.e., penicillin, erythromycin) is increasing over time. This systematic review revealed that iGBS in non-pregnant adults has risen in the last few years and has become a serious public health threat especially in older adults with underlying conditions. Given the current serotype distribution, vaccines including serotypes predominant among non-pregnant adults (i.e., serotypes V, Ia, II, and III) in their formulation are needed to provide breadth of protection. Continued surveillance monitoring potential changes in serotype distribution and antimicrobial resistance patterns are warranted to inform public health interventions.

Normal Reference Range for Serum TSH, Free T4, Total T4, and Total T3 on Roche® Platforms in Basrah, Iraq

Background: Thyroid function tests are mandatory in clinical practice because symptoms and signs are not reliable to discriminate between various types of thyroid disease.&#x0D; Aim: The aim of this study was to determine assay-specific reference range for serum free T4, total T4, total T3 and TSH among healthy non-pregnant adult cohort for Roche® platforms in Basrah (Southern Iraq) from single laboratory in a tertiary center using indirect approach of the available data.&#x0D; Methods: A Cross sectional study for non-pregnant adults 19 years and above. Sera were analyzed by using cobs e411 for thyroid functions tests.&#x0D; Results: Total enrolled persons were 10,078. The 95% reference intervals for TSH were 0.20-6.50 μIU/mL, which increased with age though not linear, for free T4 were 0.8-1.70 ng/dL, for total T4 were 3.78-15.33 μg/dL, and for total T3 were 0.80-2.50 ng/mL.&#x0D; Colcusion: Cobs e411(Roche® analytical platform) analyzer reference range for thyroid function cannot be applied for Iraqi population .

Invasive Group B Streptococcus Infections in Adults, England, 2015-2016.

During 2015–2016, a total of 3,156 episodes of invasive group B Streptococcus (iGBS) infection in adults (>15 years of age) were recorded in England, corresponding to an annual incidence of 3.48/100,000 population. iGBS incidence was highest in older patients and women of childbearing age. The 493 pregnancy-related iGBS episodes correspond to a rate of 1.34/10,000 live births. In adults up to 60–69 years of age and in pregnant women, iGBS incidence increased with higher levels of socioeconomic deprivation. Hospital admissions associated with iGBS were predominantly emergency admissions (73% [2,260/3,099]); only 7% of nonpregnancy iGBS diagnoses were made >48 hours after admission. Underlying conditions were highly prevalent in nonpregnant adult case-patients, including cardiovascular (57%), lung (43%), and kidney (45%) disease and diabetes (40%). Post-iGBS episode 30-day and 12-month all-cause mortality rates in nonpregnant adults were 12% and 24%, respectively. No pregnancy-related iGBS deaths were identified.

Insulin Therapy in Adults with Type 1 Diabetes Mellitus: a Narrative Review.

Here, we review insulin management options and strategies in nonpregnant adult patients with type 1 diabetes mellitus (T1DM). Most patients with T1DM should follow a regimen of multiple daily injections of basal/bolus insulin, but those not meeting individual glycemic targets or those with frequent or severe hypoglycemia or pronounced dawn phenomenon should consider continuous subcutaneous insulin infusion. The latter treatment modality could also be an alternative based on patient preferences and availability of reimbursement. Continuous glucose monitoring may improve glycemic control irrespective of treatment regimen. A glycemic target of glycated hemoglobin < 7% (53 mmol/mol) is appropriate for most nonpregnant adults. Basal insulin analogues with a reduced peak profile and an extended duration of action with lower intraindividual variability relative to neutral protamine Hagedorn insulin are preferred. The clinical advantages of basal analogues compared with older basal insulins include reduced injection burden, better efficacy, lower risk of hypoglycemic episodes (especially nocturnal), and reduced weight gain. For prandial glycemic control, any rapid-acting prandial analogue (aspart, glulisine, lispro) is preferred over regular human insulin. Faster-acting insulin aspart is a relatively new option with the advantage of better postprandial glucose coverage. Frequent blood glucose measurements along with patient education on insulin dosing based on carbohydrate counting, premeal blood glucose, and anticipated physical activity is paramount, as is education on the management of blood glucose under different circumstances.Plain Language Summary: Plain language summary is available for this article.

145. Liver Steatosis as a Risk Factor for Invasive Group B Streptococcus Infection in Non-Pregnant Adults

BackgroundNonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease associated with metabolic syndrome and systemic changes in immune response. However, the impact of NAFLD on bacterial infections is unknown. Group B Streptococcus (GBS) infection is a significant cause of invasive disease among adult non-pregnant patients with high mortality rates, associated with diabetes mellitus and obesity as the most common underlying conditions. The aim of this study was to analyze the association of liver steatosis with invasive GBS disease outcomes.MethodsA retrospective, cohort study of all non-pregnant adult patients diagnosed with invasive GBS infection (GBS isolated from the normally sterile site) was conducted at the University Hospital for Infectious Diseases Zagreb during a 14-year period.ResultsOf the 127 patients with invasive GBS, 90 had complete data and were included in the study. Disease primarily presented as bacteremia without focus (34; 37.8%), cellulitis/erysipelas (27; 30.0%), pneumonia (11; 12.2%) and endocarditis (8; 8.9%). The most common co-morbidities were diabetes (36; 40.0%), dyslipidemia (35; 38.9%), cardiovascular (32; 35.6%), peripheral vascular disease (18; 20.0%) and malignancy (16; 17.8%). Based upon the results of abdominal US the patients were divided into two groups: with steatosis (39; 43.3%) and without steatosis (51; 56.6%). The patients with liver steatosis were younger (63 ± 13 vs. 71 ± 14 years, P = 0.01), had higher AST (45.0; IQR 30–71 vs. 28.5; IQR 20–71, P = 0.047) and ALT (38; 25.5–55.5 vs. 21.5; 14–40, P = 0.009). There were no differences in clinical presentation and comorbidities between groups. The in-hospital mortality was 43.5% in patients with steatosis (17/39) and 17.6% (9/51) in control group (P = 0.009). Logistic regression analysis showed that endocarditis (OR 200.8; 95% CI 11.5–3512.5), primary bacteremia (6.5; 1.7–25.0), qSOFA ≥2 (20.2; 4.2–97.6) and liver steatosis (8.4; 2.0–35.1) were associated with in-hospital mortality.ConclusionOur findings showed that invasive GBS disease has significant mortality, which is independently associated with liver steatosis.Disclosures All authors: No reported disclosures.

1012. Group B Streptococcus Bacteremia in Non-Pregnant Adults in a Tertiary Care Hospital Between 2008 and 2017 in Korea

BackgroundGroup B streptococcus (GBS) has emerged as an important cause of invasive infection in nonpregnant adults. This study aimed to describe the clinical characteristics and risk factors associated with GBS bacteremia in nonpregnant adult patients in Korea.MethodsOur retrospective study reviews the hospital records of nonpregnant adults, aged ≥18 years, with GBS bacteremia who attended the Pusan National University Hospital between January 1, 2008 and December 31, 2017. The presence of underlying diseases, such as cardiovascular diseases, diabetes mellitus, malignancy, liver disease and/or alcohol abuse and renal disease, as well as possible portals of entry of infection, was analyzed.ResultsDuring the period of 10 years, there were 79 patients with GBS bacteremia. In 47 episodes (59.5%), patients were aged 60 years or older and 43 (54.4%) episodes occurred in females. Their mean age was 61 years (range, 19–91 years) and 70 patients (88.6%) had underlying diseases. Cardiovascular diseases (n = 35, 44.3%) were the most common underlying conditions, and diabetes mellitus (n = 27, 34.2%) and nonhematologic malignancy (n = 27, 34.2%) were second. Genitourinary cancer composed nearly half of nonhematologic malignancy (n = 13, 48.1%). The other comorbid conditions were liver disease and/or alcohol abuse (n = 14, 17.7%), renal disease (n = 13, 16.5%) and hematologic malignancy (n = 7, 8.9%). The most common clinical syndrome was primary bacteremia (n = 31, 39.2%). The others were bone and joint infection (n = 15, 19.0%), urinary tract infection (n = 12, 15.2%), skin and soft-tissue infection (n = 7, 8.9%), infective endocarditis (n = 4, 5.1%), peritonitis (n = 4, 5.1%), and meningitis (n = 2, 2.5%). The overall mortality rate was 13.9%, all patients had at least one underlying disease. The mortality rate of primary bacteremia was significantly higher than those of bacteremia with focus (29.0% vs. 4.2%, respectively; P = 0.002). Hematologic malignancy, liver disease, and/or alcohol abuse and renal disease were significantly associated with the primary bacteremia.ConclusionGBS bacteremia is a significant problem in nonpregnant patients, especially primary bacteremia resulted in a high rate of mortality (29%). Hematologic malignancy, liver disease, and/or alcohol abuse and renal disease were significantly related to primary bacteremia occurrence.Disclosures All authors: No reported disclosures.

Role of fibroblast growth factor 21 in gestational diabetes mellitus: A mini-review.

Gestational diabetes mellitus (GDM) is defined as glucose intolerance with onset or first diagnosis during pregnancy, but not to the level of being diagnostic for diabetes in a nonpregnant adult. In GDM, whole-body insulin-dependent glucose disposal decreases by 40%-60% which necessitates a 200%-250% increase in insulin secretion to maintain normoglycaemia. GDM develops when a pregnant woman does not produce sufficient insulin to compensate for the reduced glucose disposal. Fibroblast growth factor 21 (FGF21) is a hormone that is expressed predominantly in the liver, but also in other metabolically active tissues such as pancreas, skeletal muscle and adipose tissue. In animals, FGF21 lowers blood glucose levels and inhibits glucagon secretion. In humans, circulating FGF21 levels are increased in insulin-resistant morbidities such as obesity and type 2 diabetes mellitus (T2DM). An elevated FGF21 level is also an independent predictor of T2DM. GDM and T2DM are proposed to have similar underlying pathophysiologies, raising the question of whether a similar relationship exists between FGF21 and GDM as it does with T2DM. There are a limited number of studies investigating FGF21 levels in patients with GDM. Moreover, recent clinical trials investigating the therapeutic potential of FGF21 have highlighted a major gap in our understanding of the biology of FGF21. This review evaluates what is currently known about FGF21 and GDM and highlights important gaps that warrant further research.

Effects of Long-Term Low-Molecular-Weight Heparin on Fractures and Bone Density in Non-Pregnant Adults: A Systematic Review With Meta-Analysis.

Adults who require long-term anticoagulation with low-molecular-weight heparin (LMWH) such as cancer patients or the elderly may be at increased risk of fractures. To determine the effects of LMWH therapy of at least 3months' duration on fractures and bone mineral density (BMD) in non-pregnant adult populations. We systematically reviewed electronic databases (e.g., MEDLINE, EMBASE), conferences and bibliographies until June 2015 and included comparative studies in non-pregnant adult populations that examined the effects of LMWH (≥3months) on fractures and BMD. We synthesized evidence qualitatively and used random-effects meta-analysis to quantify the effect of LMWH on fractures. Sixteen articles reporting 14 studies were included: 10 clinical trials (n = 4865 participants) and four observational cohort studies (3 prospective, n = 221; 1 retrospective, n = 30). BMD and fractures were secondary outcomes in the majority of trials, while they were primary outcomes in the majority of observational studies. In participants with venous thromboembolism and underlying cardiovascular disease or cancer (5 RCTs, n = 2280), LMWH for 3-6 months did not increase the relative risk of all fractures at 6-12 months compared to unfractionated heparin, oral vitamin K antagonists or placebo [pooled risk ratio (RR) = 0.58, 95 % CI: 0.23-1.43; I(2) = 12.5%]. No statistically significant increase in the risk of fractures at 6-12 months was found for cancer patients (RR = 1.08, 95 % CI: 0.31-3.75; I(2) = 4.4%). Based on the data from two prospective cohort studies (n = 166), LMWH for 3-24 months decreased mean BMD by 2.8-4.8% (depending on the BMD site) compared to mean BMD decreases of 1.2-2.5% with oral vitamin K antagonists. LMWH for 3-6 months may not increase the risk of fractures, but longer exposure for up to 24months may adversely affect BMD. Clinicians should consider monitoring BMD in adults on long-term LMWH who are at increased risk of bone loss or fracture.

Group B Streptococcal Septic Arthritis of the Shoulder and Potential Association with Pelvic Examination and PAP Smear.

Group B streptococcal (GBS) infection of a native joint in a nonpregnant adult is uncommon. While many women are colonized with this flora, it rarely becomes pathogenic in its adult host. GBS associated joint infections have been reported, most of which have been related to hematogenous seeding from unknown sources. To our knowledge, there are no published case reports of a GBS joint infection in association with a pelvic exam and Papanicolaou (PAP) smear. In this case report, we present a case of GBS sepsis of a native shoulder, possibly resulting from a routine pelvic exam and PAP smear.

Evaluation of point-of-care maternal venous lactate testing in normal pregnancy

Objective: There is little information about whether the established non-pregnant adult venous lactate reference range is appropriate for pregnancy. This prospective observational study examined whether the non-pregnant adult reference range is appropriate during pregnancy.Methods: Women attending for routine prenatal appointments or elective cesarean delivery in a tertiary hospital were recruited. Clinical details were recorded and venous lactate concentration was measured using a point-of-care (POC) device.Results: Of the 246 women, 199 were 6–18 weeks’ gestation and 47 were 36–42 weeks’ gestation. Mean lactate concentration was within the non-pregnant reference range in early and late pregnancy (0.86 SD ± 0.46 mmol/L and 1.15 SD ± 0.40 mmol/L, respectively). The mean time between phlebotomy and result was 6.1 SD ± 1.7 min. There was no correlation between lactate levels and either maternal age or time interval from tourniquet placement to lactate measurement. In women of 6–18 weeks’ gestation positive bivariate relationships were found between lactate and BMI (p = 0.03, r = 0.158), earlier gestational age (p = 0.04, r= −0.145), and smoking (p = 0.01, r = 0.183), but these were not found in late pregnancy.Conclusions: The venous lactate reference range for the non-pregnant adult may be applied in pregnancy. Further studies should examine lactate dynamics in labor and postpartum.

Development of a pregnant woman phantom using polygonal mesh, for dosimetric evaluations

Due to the embryo/fetus radiosensitivity the accurate estimation of the absorbed dose distribution in the abdominal area is an additional problem caused by the exposure of pregnant women to ionizing radiation in medical applications. This paper reports the construction and insertion of a fetal representation in a female geometry by means of 3D modeling techniques. In order to characterize an ECM the Grupo de Dosimetria Numerica (GDN) is using, mainly, simulators emitting gama sources and voxel phantoms coupled to a MC code. The phantoms are predominantly constructed from stacks of magnetic resonance images (MRI), computed tomography (CT) (obtained from scans of real patients) or from 3D modeling techniques. Due to the difficulty of obtaining medical images of pregnant women, 3D objects in several formats (.obj, .max, .blend, etc.) were acquired for anatomical representation of a non-pregnant adult. To construct a fetal representation, the 3D modeling technique called Poly Modeling (polygon mesh) was used inside of the software Autodesk 3ds Max 2014 (free student version). Information about the radiosensibility of organs included in the abdominal area will be used to fit and use the pregnant phantom in numerical dosimetry. For this, the phantom will be voxelized and the masses of organs of interest will be adjusted according to data provided by International Commission on Radiological Protection (ICRP). Finally, the phantom will be coupled to a MC code creating a MCE that will serve as base for the construction of several other models involving pregnant women submitted to ionizing radiation.

Invasive Group B Streptococcal Disease in Non-pregnant Adults, Réunion Island, 2011

While the prevalence of Group B streptococcus (GBS) colonization is important, little is known about invasive GBS (iGBS) disease in tropical areas. Our objective was to assess the burden of iGBS disease among non-pregnant adults. A prospective hospital-based study of all non-pregnant adult patients with iGBS disease was conducted between January and December 2011 in Saint Pierre, Réunion Island, to assess its cumulative incidence rate (CIR). Capsular serotyping and multilocus sequence typing were performed to characterize GBS isolates. Case-control study was done to identify risk factors. The overall CIR of iGBS disease was 10.1 per 100,000. The CIR in elderly patients (≥ 65 yrs) was estimated at 40.6 per 100.000, and that of adults (15-64 years) at 6.7 per 100.000. Aboriginal origin in the Indian Ocean and overweight were both associated with iGBS disease. The most prominent clinical forms were osteo-articular and skin/soft tissue infections, as a consequence of diabetic foot. The serotypes were classic, type-Ia being the most prevalent. The hyper virulent ST-17 (CC17) was associated with type-III. The incidence of iGBS disease found in Réunion island is twofold that usually reported. This burden is linked to overweight in aboriginal people from the Indian Ocean.

Current Status of Vaccine Development for Group B Streptococcus

The incidence of neonatal early-onset sepsis due to group B Streptococcus (GBS) has decreased with the use of intrapartum antibiotic prophylaxis, but GBS infection remains a significant clinical concern. Early-onset disease still occurs among term infants born to women falsely screened GBS-negative, and premature infants still disproportionately suffer from both early-onset and late-onset GBS infection. In addition, there is no current strategy for preventing GBS disease among elderly and immunocompromised, nonpregnant adults. The development of GBS vaccines with efficacy across serotypes may address many of the clinical gaps left by GBS intrapartum antibiotic prophylaxis. Multiple preclinical and human phase I studies have been completed demonstrating the safety and immunogenicity of candidate glycoconjugate GBS vaccines. Phase III vaccine trials are needed to determine the clinical efficacy of maternal and nonpregnant adult vaccination.

Glucagon-like peptide-1 receptor agonists as add-on therapy to basal insulin in patients with type 2 diabetes: a systematic review

The prevalence of obesity and diabetes continues to rise in the US. Glucagon-like peptide-1 receptor agonist (GLP-1RA) is an effective treatment option for type 2 diabetes mellitus (T2DM) that promotes weight loss. Common and effective treatment options added to metformin therapy (basal insulin, sulfonylureas, and pioglitazone) contribute to weight gain, which makes the addition of GLP-1RAs advantageous. Exenatide was the first agent in this class and has recently been approved for use in combination with insulin glargine by the US Food and Drug Administration and the European Medicines Agency. Until recently, there was a lack of data examining basal insulin combined with these agents. The main purpose of this article is to review the prospective interventional data on the safety and efficacy of GLP-1RAs (exenatide, liraglutide, albiglutide, lixisenatide) combined with basal insulin therapy in nonpregnant adults with T2DM. Databases searched were PubMed, Cochrane Central Register of Controlled Trials and the Database of Systematic Reviews (inception to January 2012). s presented at relevant diabetes and endocrine meetings from 2009 to 2011 were also reviewed, as were reference lists of identified publications. A total of five studies met the criteria and were included in the review. Data from these studies demonstrated that this combination therapy offers advantages for the treatment of diabetes, such as additional lowering of A1c without major risk for hypoglycemia, lower basal insulin requirements, decreased postprandial glucose levels (with or without fasting plasma glucose decreases), and weight loss, or at the very least, less weight gain. However, the gastrointestinal side effects and high cost of these agents may limit their use. This review demonstrates that adding a GLP-1RA to an existing basal insulin regimen is a reasonable treatment strategy in nonpregnant adult patients with T2DM.

Pharmacokinetics of intravenous theophylline in pregnant patients at term.

The pharmacokinetics of theophylline was determined in six pregnant, nonsmoking women in labor at term following a single bolus infusion of 5.6 mg/kg of aminophylline over 20 minutes. Cord blood levels were obtained from three babies at delivery. Compared to values reported in the literature for nonpregnant adult nonsmokers, the volume distribution (mean 573 +/- 53 ml/kg) and clearance rate (mean .88 +/- .24 ml/kg/min) of theophylline is increased in pregnant women, but the half-life (mean 7.95 +/- 2 hrs) remains unaltered. Similar doses of aminophylline can therefore be used in pregnant and nonpregnant adults who do not smoke cigarettes, but the infusion rate required to maintain a mean serum concentration of 10 micrograms/ml (0.5 mg/kg/hr) is almost half that initially reported in the literature. The serum theophylline concentrations in maternal venous and mixed cord blood at delivery were almost identical, which implies that theophylline crosses the placenta rapidly and that the fetus represents a "shallow" drug compartment.

Antimalarial dosing regimens and drug resistance

The contribution of underdosing to antimalarial treatment failure has been underappreciated. Most recommended dosage regimens are based on studies in non-pregnant adult patients. Young children and pregnant women, who bear the heaviest malaria burden, have the highest treatment failure rates. This has been attributed previously to lower immunity, although blood concentrations of many antimalarial drugs are significantly lower in pregnant women and young children than in non-pregnant adults. Nevertheless, there have been no studies of higher dosages. Sub-therapeutic concentrations will certainly contribute to poorer responses to treatment and will fuel the emergence and spread of antimalarial drug resistance. There is an urgent need for studies to optimise antimalarial dosage regimens in infants, young children and pregnant women, both to improve cure rates and to prolong the useful therapeutic lives of antimalarial drugs.

Reversal of pregnancy-mediated plasma hypotonicity in the near-term rat

Objective: Maternal plasma hypotonicity occurs early in rat and human pregnancy with resetting of the plasma osmolality threshold for vasopressin secretion and thirst. In humans, amniotic fluid volumereaches maximum levels in the mid-third trimester and decreases thereafter. We hypothesized that a reversal of maternal plasma hypotonicity occurs near term, contributing to reduced fetal and amniotic fluidwater content.Methods: Maternal plasma and amniotic fluid osmolality and sodium levels, including amniotic fluid volume, were measured at 16, 18 and 20 days of rat gestation. Additionally, maternaland fetal brains were analyzed for water and electrolyte content. Non-pregnant adult female rats represented controls.Results: Compared to non-pregnant adults, 16-day and 18-day pregnant ratshad significantly lower plasma osmolality (301.0 ± 2.3 vs. 295.4 ± 2.8 and 289.7 ± 3.3 mOsm/kg, respectively) and sodium levels (140.3 ± 1.0 vs. 135.7 ± 0.8 and 133.4± 1.4 mEq/l, respectively). Conversely, 20-day pregnant rats showed no significant difference in plasma osmolality (298.4 ± 3.1 mOsm/kg) or sodium levels (137.6 ± 1.0 mEq/l) from non-pregnantadults. With advancing gestation, the amniotic fluid volume decreased whereas the osmolality and sodium levels increased significantly. Maternal brain water content was significantly higher in 16-day and18-day pregnant rats compared to control rats (78.7 ± 0.1 and 78.1 ± 0.2 vs. 76.9 ± 0.2% wet weight) and returned to non-pregnant values in the 20-day pregnant rats (76.6 ± 0.2%).In association with the maternal changes, fetal brain water and electrolyte content significantly decreased from 16-day to 18-day to 20-day fetuses.Conclusion: These findings indicate a reversalof maternal plasma hypotonicity and reduced maternal brain water content in the near-term pregnant rat. We speculate that relative maternal plasma hypertonicity near term may contribute to reduced amnioticfluid volume.