Quality Initiative to Reduce Failed Trial of Labor after Cesarean Using Calculated VBAC Success Likelihood.

OBJECTIVE: Vaginal birth after cesarean can reduce morbidity associated with multiple cesarean deliveries. Failed vaginal birth after cesarean is associated with increased maternal and neonatal morbidity. The Maternal-Fetal Medicine Units Vaginal Birth After Cesarean calculator is a validated tool to predict the likelihood of successful trial of labor after cesarean. Predicted likelihood < 60% has been associated with increased maternal and neonatal morbidity. We sought to determine if formal incorporation of calculated vaginal birth after cesarean likelihood into patient-centered counseling would reduce failed vaginal birth after cesarean. STUDY DESIGN: This is a quality improvement intervention at a single tertiary-care academic medical center, in which standardized patient counseling was implemented, facilitated by an electronic medical record template featuring patient-specific likelihood of vaginal birth after cesarean success. Term singleton pregnancies with history of one to two cesareans were included; those with contraindication to labor were excluded. Historical controls (January 2016-December 2018, n = 693) were compared with a postimplementation cohort (January 2019-April 2020, n = 328). Primary outcome was failed vaginal birth after cesarean. RESULTS: Fewer patients in the postintervention cohort had a history of an arrest disorder (PRE: 48%, 330/693 vs. POST: 40%, 130/326, p = 0.03); demographics were otherwise similar, including the proportion of patients with <60% likelihood of success (PRE: 39%, 267/693, vs. POST: 38%, 125/326). Following implementation, induction of labor in patients with a <60% likelihood of successful vaginal birth after cesarean decreased from 17% (45/267) to 5% (6/125, p < 0.01). The proportion of failed vaginal birth after cesarean decreased from 33% (107/329) to 22% (32/143, p = 0.04). Overall vaginal birth after cesarean rate did not change (PRE: 32%, 222/693, vs. POST: 34%, 111/326, p = 0.52). CONCLUSION: An intervention targeting provider counseling that included a validated vaginal birth after cesarean success likelihood was associated with decreased risk of failed trial of labor after cesarean without affecting overall vaginal birth after cesarean rate. KEY POINTS: · Labored cesarean increases maternal morbidity.. · Application of the Maternal-Fetal Medicine Units (MFMU) calculator to antenatal counseling decreased labored cesarean.. · Application of the MFMU calculator to antenatal counseling did not decrease overall vaginal birth after cesarean rate..

Detection of SARS-CoV-2 in Neonatal Autopsy Tissues and Placenta.

Severe coronavirus disease in neonates is rare. We analyzed clinical, laboratory, and autopsy findings from a neonate in the United States who was delivered at 25 weeks of gestation and died 4 days after birth; the mother had asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and preeclampsia. We observed severe diffuse alveolar damage and localized SARS-CoV-2 by immunohistochemistry, in situ hybridization, and electron microscopy of the lungs of the neonate. We localized SARS-CoV-2 RNA in neonatal heart and liver vascular endothelium by using in situ hybridization and detected SARS-CoV-2 RNA in neonatal and placental tissues by using reverse transcription PCR. Subgenomic reverse transcription PCR suggested viral replication in lung/airway, heart, and liver. These findings indicate that in utero SARS-CoV-2 transmission contributed to this neonatal death.

Safety-Related Outcomes of Novel mRNA COVID-19 Vaccines in Pregnancy.

OBJECTIVE: The objective of this study was to describe the safety profile and demographic data for a cohort of pregnant individuals who received an mRNA coronavirus disease 2019 (COVID-19) vaccine. STUDY DESIGN: Prospective cohort study (with exposure matching) of individuals with active pregnancy who underwent immunization with a novel mRNA COVID-19 vaccine matched 1:2 with vaccinated age-matched female nonregnant controls was carried out. The primary outcome was defined as any vaccine-related complaints as defined in the original safety data. Secondary outcomes included specific complaints, COVID-19 screening test, and positive COVID-19 test. RESULTS: Eighty-three vaccinated pregnant persons were age-matched with 166 female controls, all of whom were vaccinated between December 2020 and January, 2021. There was no difference in race or ethnicity between the groups. The mean body mass index of pregnant patients was lower than that of controls (26.1 vs. 29.2, p = 0.002). The frequency of complaints following vaccine administration was not different between pregnant and nonpregnant patients (18.1 vs. 16.9%, p = 0.201). Pregnant individuals were more likely to report fever (4.8 vs. 0.6%, p = 0.044) and gastrointestinal symptoms (4.8 vs. 0%, p = 0.012). CONCLUSIONS: Side effect profiles of COVID-19 vaccine administration at our institution were relatively similar between pregnant and nonpregnant individuals and no serious complications occurred in either group. As COVID-19 infection in pregnancy can have significant morbidity, our data support the continued use of the vaccine for pregnant patients. KEY POINTS: · Pregnant and nonpregnant women had a similar frequency of complaints.. · No serious adverse outcomes were observed in either group.. · Pregnant women were more likely to report fever and gastrointestinal side effects which may reflect gestationally mediated physiological responses to immunization..

Maternal Secretor Status Affects Oral Rotavirus Vaccine Response in Breastfed Infants in Bangladesh.

Secretor status controls mucosal histo-blood group antigen expression and is associated with susceptibility to rotavirus (RV) diarrhea, with nonsecretors less susceptible to symptomatic infection. The role of breast milk secretor status on oral live-attenuated RV vaccine response in breastfed infants has not been explored. In a monovalent G1P[8] RV vaccine (Rotarix) trial in Bangladesh, RV-specific plasma immunoglobulin A antibody seroconversion rates were higher among infants of maternal nonsecretors (39%) than infants of maternal secretors (23%; P = .001). Maternal status remained a significant predictor when correcting for infant status (P = .002). Maternal secretor status should be considered when interpreting oral RV vaccine responses in low- and middle-income settings. Clinical Trials Registration. NCT01375647.

Postnatal craniofacial ontogeny in neandertals and modern humans.

OBJECTIVES: Neandertals and humans are closely related but differ noticeably in adult morphology. Previous work has been equivocal as to the contribution of postnatal growth and development to these differences. Due to disparate preservation, most analyses focus on specific anatomies, reconstructed fossils, or limited sample sizes. The objective of this research is to highlight the importance of postnatal growth in expressing Neandertal-human distinctions in the craniofacial skeleton, using a large and unreconstructed Neandertal sample. MATERIALS/METHODS: A resampling approach is utilized to compare relative size change in 20 craniofacial dimensions between Neandertals (n = 42) and humans (n = 262). The large number of immature Neandertal samples within and between dental stages provides the necessary variation to test for growth differences. Nested resampling using human-human comparisons assesses the likelihood of observing human-Neandertal growth differences under the null hypothesis of similar ontogenetic variation. RESULTS: Humans and Neandertals undergo comparable levels of overall size change. However, we identify growth differences for a number of traits, helping explain some of the unique features of this fossil taxon. Nested resampling shows it is unlikely that a Neandertal-like maturation would be observed in a random ontogenetic sample of humans. DISCUSSION: Growth during adolescence appears to be fundamental in the expression of some Neandertal anatomies. Neandertal upper facial and nasal breadths appear to have expanded rapidly after puberty to account for differences between preadolescents and adults, and Neandertals and humans. Mandibular growth differences may relate to anterior tooth use to process foods and paramastication during Neandertal maturation.

Obstetrical Outcomes of Ultrasound Identified Uterine Fibroids in Pregnancy.

Objective We aimed to determine if fibroids in pregnancy, categorized by size, are associated with adverse obstetrical outcomes. Study Design Demographic, clinical, and delivery data were collected from charts of women with singleton gestations who delivered at >20 weeks gestation with fibroids identified at routine anatomy scan and their randomly selected age-matched controls. Largest fibroid diameter was used to categorize small fibroids (≤5 cm) and large fibroids (>5 cm). Results We included 450 patients: 264 patients with fibroids (174 small, 90 large fibroids) and 186 age-matched controls. Women with large fibroids had significantly greater blood loss than women with small fibroids and women with no fibroids (p-value <0.0001 and <0.0001 after adjusting for delivery mode). When fibroid size was compared individually, there was a significantly higher rate of primary cesarean section in both small and large fibroid groups when compared with women with no fibroids (p-values 0.044 and 0.003 after adjusting for body mass index). Conclusion Women with fibroids in pregnancy have higher rates of primary cesarean delivery and are at significant risk for increased blood loss at the time of delivery.

Moving toward implementation: the potential for accountable care organizations and private-public partnerships to advance active neighborhood design.

The 2010 Affordable Care Act's (ACA) aims of lowering costs and improving quality of care will renew focus on preventive health strategies. This coincides with a trend in medicine to reconsider population health approaches as part of the standard curriculum. This intersection of new policy and educational climates presents a unique opportunity to reconsider traditional healthcare structures. This paper introduces and advances an alignment that few have considered. We propose that accountable care organizations (ACOs), which are expected to proliferate under the ACA, present the best opportunity to establish partnerships between healthcare, public health, and community-based organizations to achieve the legislation's goals. One example is encouraging daily physical activity via built environment interventions and programs, which is recommended by numerous groups. We highlight how nonprofit organizations in Sacramento, California have been able to leverage influence, capital, and policy to encourage design for active living, and how their work is coordinating with public health and healthcare initiatives. In conclusion, we critically examine potential barriers to the success of partnerships between ACOs and community organizations and encourage further exploration and evaluation.

Dietary reconstruction of Pliocene Parapapio whitei from Makapansgat, South Africa, using dental microwear texture analysis.

Pliocene Parapapio whitei fossils from Makapansgat have yielded stable isotope values suggesting some foraging on C4 plants and possibly underground storage organs (USOs). Dental microwear texture analysis on Pp.whitei (M 3147, MP 62, MP 223 and MP 239) from Makapansgat Members 3-4 is performed to examine whether tooth surface damage from mastication agrees with prior dietary inferences from isotopes. The enamel surface texture of Pp. whitei is relatively complex, resembling Lophocebus albigena and Cebusapella, and lacks the anisotropy of Trachypithecuscristatus and Alouattapalliata. The textural fill volume of Pp. whitei is distinct from extant forest primates suggesting extremes in hard-object consumption. Grit adhering to USOs is offered as an explanation for these enamel textural properties, corroborating the inference that Pp. whitei supplemented its diet with terrestrial resources. © 2013 S. Karger AG, Basel.

Protocol-driven primary care and community linkages to improve population health in rural Zambia: the Better Health Outcomes through Mentoring and Assessment (BHOMA) project.

INTRODUCTION: Zambia's under-resourced public health system will not be able to deliver on its health-related Millennium Development Goals without a substantial acceleration in mortality reduction. Reducing mortality will depend not only upon increasing access to health care but also upon improving the quality of care that is delivered. Our project proposes to improve the quality of clinical care and to improve utilization of that care, through a targeted quality improvement (QI) intervention delivered at the facility and community level. DESCRIPTION OF IMPLEMENTATION: The project is being carried out 42 primary health care facilities that serve a largely rural population of more than 450,000 in Zambia's Lusaka Province. We have deployed six QI teams to implement consensus clinical protocols, forms, and systems at each site. The QI teams define new clinical quality expectations and provide tools needed to deliver on those expectations. They also monitor the care that is provided and mentor facility staff to improve care quality. We also engage community health workers to actively refer and follow up patients. EVALUATION DESIGN: Project implementation occurs over a period of four years in a stepped expansion to six randomly selected new facilities every three months. Three annual household surveys will determine population estimates of age-standardized mortality and under-5 mortality in each community before, during, and after implementation. Surveys will also provide measures of childhood vaccine coverage, pregnancy care utilization, and general adult health. Health facility surveys will assess coverage of primary health interventions and measures of health system effectiveness. DISCUSSION: The patient-provider interaction is an important interface where the community and the health system meet. Our project aims to reduce population mortality by substantially improving this interaction. Our success will hinge upon the ability of mentoring and continuous QI to improve clinical service delivery. It will also be critical that once the quality of services improves, increasing proportions of the population will recognize their value and begin to utilize them.

Utility of Weekly Laboratory Monitoring in the Expectant Management of Hypertensive Disorders of Pregnancy.

Our retrospective cohort study evaluates the diagnostic yield of weekly laboratory surveillance in outpatient management of hypertensive disorders of pregnancy (HDP) based on patient clinical status at the time of laboratory testing. The study included 459 patients and 1,082 laboratory episodes: 356 (32.9%) episodes were performed in the setting of concerning clinical findings and 726 (67.1%) when the patient was asymptomatic. Overall, the diagnostic yield for abnormal laboratory values (n=11) was 1.0% (95% CI 0.4-1.6%) of all assessments performed and 2.4% (95% CI 1.0-3.8%) among all patients in the cohort. The prevalence of abnormal test results was higher in patients with clinical findings (2.8%, 95% CI 1.1-4.5%) compared with those who were asymptomatic (0.1%, 95% CI 0-0.2%) ( P <.01). Clinical findings suggestive of worsening disease had a 91% sensitivity (95% CI 59-100%) and a 99% (95% CI 99-100%) negative predictive value for abnormal laboratory values. Directed screening based on signs and symptoms, rather than universal weekly screening, may be a potential strategy to lower costs and reduce multiple blood draws for patients with HDP, because there is a low diagnostic yield for this practice.

Masked pregnancy-associated hypertension as a predictor of adverse outcomes.

BACKGROUND: Masked hypertension has been described in nonpregnant populations as elevated blood pressure in the home setting that is not reproduced on clinical assessment. Patients with masked hypertension have a greater risk of cardiovascular morbidity than patients who have blood pressures within normal range or those with white coat hypertension. OBJECTIVE: This study aimed to determine whether masked pregnancy-associated hypertension detected on Connected Maternity Online Monitoring, a remote home blood pressure monitoring system, is associated with higher rates of hypertensive disorders of pregnancy during delivery admission and maternal and neonatal morbidities. STUDY DESIGN: This was a retrospective cohort study of all patients on Connected Maternity Online Monitoring who delivered at 6 hospitals in a single healthcare system between October 2016 and December 2020. Patients were classified as having either normal blood pressure or masked pregnancy-associated hypertension. Masked pregnancy-associated hypertension was defined as remotely detected systolic blood pressure of ≥140 mm Hg or diastolic blood pressure of ≥90 mm Hg after 20 weeks of gestation on 2 occasions before diagnosis in a clinical setting. The chi-square test and Student t test were used for demographic and outcomes comparisons. Logistic regression was used to adjust outcomes by race, insurance, and body mass index. RESULTS: A total of 2430 deliveries were included in our analysis, including 165 deliveries that met the criteria for masked pregnancy-associated hypertension. Clinically established pregnancy-associated hypertension, defined at the time of delivery, was more common in the masked pregnancy-associated hypertension group than in the normotensive group (66% vs 10%; adjusted odds ratio, 17.2; 95% confidence interval, 11.91-24.81). Patients with masked pregnancy-associated hypertension had higher rates of preeclampsia with severe features on delivery admission than normotensive patients (28% vs 2%; adjusted odds ratio, 23.35; 95% confidence interval, 14.25-38.26). Preterm delivery (16% vs 7%; adjusted odds ratio, 2.47; 95% confidence interval, 1.55-3.94), cesarean delivery(38% vs 26%; adjusted odds ratio, 1.58; 95% confidence interval, 1.13-2.23), small for gestational age (11% vs 5%; adjusted odds ratio, 2.27; 95% confidence interval, 1.31-3.94), and neonatal intensive care unit admission (8% vs 4%; adjusted odds ratio, 2.20; 95% confidence interval, 1.18-4.09) were more common among patients with masked pregnancy-associated hypertension than among normotensive patients. CONCLUSION: With more outcomes research, remote blood pressure monitoring may prove to be an important tool in identifying pregnancies at risk of complications related to masked hypertension.

Maternal Breast Milk Secretor Phenotype Does Not Affect Infant Susceptibility to Rotavirus Diarrhea.

Breast milk secretor status is associated with antibody seroconversion to oral rotavirus vaccination. Here, we were unable to detect a similar impact on risk of infant rotavirus diarrhea or vaccine efficacy through 2 years of life, underscoring limitations of immunogenicity assessment alone in evaluation of oral rotavirus vaccine response.

MicroRNAs: Small but Key Players in Viral Infections and Immune Responses to Viral Pathogens.

Since the discovery of microRNAs (miRNAs) in C. elegans in 1993, the field of miRNA research has grown steeply. These single-stranded non-coding RNA molecules canonically work at the post-transcriptional phase to regulate protein expression. miRNAs are known to regulate viral infection and the ensuing host immune response. Evolving research suggests miRNAs are assets in the discovery and investigation of therapeutics and diagnostics. In this review, we succinctly summarize the latest findings in (i) mechanisms underpinning miRNA regulation of viral infection, (ii) miRNA regulation of host immune response to viral pathogens, (iii) miRNA-based diagnostics and therapeutics targeting viral pathogens and challenges, and (iv) miRNA patents and the market landscape. Our findings show the differential expression of miRNA may serve as a prognostic biomarker for viral infections in regard to predicting the severity or adverse health effects associated with viral diseases. While there is huge market potential for miRNA technology, the novel approach of using miRNA mimics to enhance antiviral activity or antagonists to inhibit pro-viral miRNAs has been an ongoing research endeavor. Significant hurdles remain in terms of miRNA delivery, stability, efficacy, safety/tolerability, and specificity. Addressing these challenges may pave a path for harnessing the full potential of miRNAs in modern medicine.

Pregnancy Outcomes in Patients After Completion of the mRNA Coronavirus Disease 2019 (COVID-19) Vaccination Series Compared With Unvaccinated Patients.

OBJECTIVE: To compare frequency of perinatal death between pregnant patients who completed the mRNA coronavirus disease 2019 (COVID-19) vaccination series and unvaccinated patients. METHODS: This retrospective cohort study included 15,865 pregnant patients who delivered 16,132 newborns after 20 weeks of gestation within a large regional health system between January 1, 2021, and December 31, 2021. Patients who received two doses of mRNA vaccine (Pfizer-BioNTech [BNT162b2] or Moderna [mRNA-1273]) were included in the vaccinated group and were compared with unvaccinated patients. Exclusions included partial vaccination, viral-vector vaccine, major congenital anomalies, and higher-order multiple gestation. Our primary outcome was perinatal death, including stillbirth and neonatal death, which was evaluated by logistic regression. Unadjusted odds ratios and adjusted odds ratios (aORs) were reported, controlling for age, body mass index (BMI), diabetes, hypertension, smoking, twin gestation, and insurance status. Propensity score matching was also performed. RESULTS: A total of 15,865 patients were included in the final analysis: 2,069 in the vaccination group and 13,796 in the control group. Only 13.0% of the cohort was included in the vaccination group; however, the vaccination rate increased over the course of the study period as the vaccine became more widely available and accepted. Vaccinated patients were older, with higher rates of people of non-Black racial non-Hispanic ethnic backgrounds, people with private insurance, and those with higher BMIs. Vaccination was associated with a lower incidence of perinatal death (0.5% vaccinated group vs 0.8% unvaccinated group, aOR 0.20 0.05-0.88). Vaccination against COVID-19 was also associated with lower rates of preterm delivery (aOR 0.63, 0.48-0.82), neonates with very low birth weight (aOR 0.35, 0.15-0.84), and neonatal intensive care unit (NICU) admission (aOR 0.66, 0.52-0.85). The association between vaccination and lower rates of perinatal death was no longer significant after propensity score matching. CONCLUSION: In a large retrospective cohort study, receipt of the primary mRNA COVID-19 vaccination series was associated with a lower rate of several adverse pregnancy outcomes, including perinatal death, preterm delivery, neonates with very low birth weight, and NICU admission. Although the decreased rates of perinatal death did not remain significant after propensity score matching, there was evidence of directional benefit for vaccinated patients.

Preclinical efficacy and safety of novel SNAT against SARS-CoV-2 using a hamster model.

To address the unprecedented global public health crisis due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we designed and developed a novel antiviral nano-drug, called SNAT (Smart Nano-Enabled Antiviral Therapeutic), comprised of taxoid (Tx)-decorated amino (NH2)-functionalized near-atomic size positively charged silver nanoparticles (Tx-[NH2-AgNPs]) that are stable for over 3 years. Using a hamster model, we tested the preclinical efficacy of inhaled SNAT on the body weight, virus titer, and histopathology of lungs in SARS-CoV-2-infected hamsters, including biocompatibility in human lung epithelium and dermal fibroblasts using lactase dehydrogenase (LDH) and malondialdehyde (MDA) assays. Our results showed SNAT could effectively reverse the body weight loss, reduce the virus load in oral swabs, and improve lung health in hamsters. Furthermore, LDH assay showed SNAT is noncytotoxic, and MDA assay demonstrated SNAT to be an antioxidant, potentially quenching lipid peroxidation, in both the human cells. Overall, these promising pilot preclinical findings suggest SNAT as a novel, safer antiviral drug lead against SARS-CoV-2 infection and may find applications as a platform technology against other respiratory viruses of epidemic and pandemic potential.

Measures of adiposity correlate with renal filtration in young nulliparous women: An observational cohort study.

OBJECTIVE: Renal hyperfiltration, which has been documented in severe obesity and obesity-associated hypertension, can occur with hypertensive disorders of pregnancy. Identification of prepregnancy risk factors for unrecognized renal hyperfiltration could inform screening and intervention strategies to protect against pregnancy complications. In young, healthy, nulliparous women, associations between associations between measures of adiposity, insulin resistance, and renal vascular resistance were thus evaluated. METHODS: This is a secondary analysis of a prospective observational trial characterizing associations of prepregnancy and late-pregnancy maternal physiology. Seventy-nine nulligravid women aged 18-42 years without major medical conditions were assessed for percent android body fat using dual-energy X-ray absorption. Renal cortical vessel blood flow resistance index (CVRI) was determined using Doppler ultrasonography. Creatinine clearance was calculated from 24-hour urine collection. RESULTS: Renal CVRI inversely correlates with body mass index (r = -0.23, p = 0.047), percent android fat (r = -0.30, p = 0.008), and supine pulse (r = -0.44, p < 0.001). Creatinine clearance is positively associated with BMI and HOMA-IR.In regression modeling, supine pulse (r2 = 0.22, p < 0.001) and cardiac index (r2 = 0.05, p = 0.045) predict renal CVRI, whereas HOMA-IR (r2 = 0.11, p = 0.008) and cardiac output (r2 = 0.06, p = 0.039) predict creatinine clearance. Measures of adiposity are not independently predictive of either measure. CONCLUSIONS: In healthy young women, measures of adiposity and insulin resistance correlate positively with renal filtration. Preclinical manifestations of renal hyperfiltration may have implications for pregnancy outcomes.

Guidelines for submitting adverse event reports for publication.

Publication of case reports describing suspected adverse effects of drugs and medical products that include herbal and complementary medicines, vaccines and other biologicals and devices is important for postmarketing surveillance. Publication lends credence to important signals raised in these adverse event reports. Unfortunately, deficiencies in vital information in published cases can often limit the value of such reports by failing to provide enough details for either (i) a differential diagnosis or provisional assessment of cause-effect association, or (ii) a reasonable pharmacological or biological explanation. Properly described, a published report of one or more adverse events can provide a useful signal of possible risks associated with the use of a drug or medical product which might warrant further exploration. A review conducted by the Task Force authors found that many major journals have minimal requirements for publishing adverse event reports and some have none at all. Based on a literature review and our collective experience in reviewing adverse event case reports in regulatory, academic and industry settings, we have identified information that we propose should always be considered for inclusion in a report submitted for publication. These guidelines have been endorsed by the International Society for Pharmacoepidemiology (ISPE) and the International Society of Pharmacovigilance (ISoP) and are freely available on the societies' web sites. Their widespread distribution is encouraged. ISPE and ISoP urge biomedical journals to adopt these guidelines and apply them to case reports submitted for publication. They also encourage schools of medicine, pharmacy, and nursing to incorporate them into the relevant curricula that address the detection, evaluation and reporting of suspected drug or other medical product adverse events.

Enzymes that synthesize the IB4 epitope are not sufficient to impart IB4 binding in dorsal root ganglia of rat.

The isolectin B4 (IB4) stains a subset of small and medium-sized dorsal root ganglion (DRG) neurons by binding to terminal alpha-galactose on glycoproteins and glycolipids. The enzymes alpha(1,3)galactosyltransferase (1,3GT) and isoglobotriaosylceramide synthase (iGb3S) synthesize the galactose-alpha(1,3)-galactose group, which is the most common carbohydrate containing terminal alpha-galactose. 1,3GT preferentially glycosylates proteins whereas iGb3S glycosylates lipids. We generated antibodies against rat 1,3GT and iGb3S that were used for immunohistochemical staining of DRG cells. Virtually all neurons that bound IB4 expressed both enzymes, suggesting that IB4 binds to both glycoproteins and glycolipids in IB4-positive neurons. 1,3GT immunoreactivity was observed in small and medium-sized neurons and satellite cells. iGb3S immunoreactivity was observed in neurons of varying sizes. Many neurons that expressed these enzymes did not bind IB4. Additionally, the majority of neurons that expressed substance P expressed both enzymes but did not bind IB4. Ultrastructual studies revealed that 1,3GT was predominantly associated with the Golgi apparatus, whereas iGb3S was found near the Golgi apparatus and in large, clear vesicles throughout the soma. These data suggest that, although expression of 1,3GT and/or iGb3S appears to be necessary for IB4 binding, expression of these enzymes is not sufficient to impart IB4 binding.

Guidelines for submitting adverse event reports for publication.

Publication of case reports describing suspected adverse effects of drugs and medical products that include herbal and complementary medicines, vaccines, and other biologicals and devices is important for postmarketing surveillance. Publication lends credence to important signals raised in these adverse event reports. Unfortunately, deficiencies in vital information in published cases can often limit the value of such reports by failing to provide enough details for either (i) a differential diagnosis or provisional assessment of cause-effect association, or (ii) a reasonable pharmacological or biological explanation. Properly described, a published report of one or more adverse events can provide a useful signal of possible risks associated with the use of a drug or medical product which might warrant further exploration. A review conducted by the Task Force authors found that many major journals have minimal requirements for publishing adverse event reports, and some have none at all. Based on a literature review and our collective experience in reviewing adverse event case reports in regulatory, academic, and industry settings, we have identified information that we propose should always be considered for inclusion in a report submitted for publication. These guidelines have been endorsed by the International Society for Pharmacoepidemiology (ISPE) and the International Society of Pharmacovigilance (ISoP) and are freely available on the societies' websites. Their widespread distribution is encouraged. ISPE and ISoP urge biomedical journals to adopt these guidelines and apply them to case reports submitted for publication. They also encourage schools of medicine, pharmacy, and nursing to incorporate them into the relevant curricula that address the detection, evaluation, and reporting of suspected drug or other medical product adverse events.