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Aim of this study was to demonstrate the influence of different analytical procedures and techniques on the resulting miRNA expression profile in healthy control subjects and tumor patients using the oral squamous cell carcinoma (OSCC) model and to demonstrate the technical and biological reproducibility. Body fluids such as saliva are suitable for non-invasive miRNA analysis because ubiquitously circulating miRNA can be found in them. It was technically possible to distinguish between healthy and diseased samples based on the miRNA expression profile found. Regardless of the methodology used, good technical reproducibility of the results seems to be achievable. On the other hand, biological reproducibility was inadequate, which is why prompt sampling and sequencing is recommended. The data indicate that malignant lesions can be detected using miRNA signatures extracted from saliva. This could stimulate further research to establish standardized protocols and kits for sample collection, miRNA extraction, sequencing and interpretation of results., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Stroke is a leading cause of mortality and disability worldwide. Although studies have primarily focused on health and functioning among stroke survivors, there is limited research on longitudinal patterns of long-term care use among older adults with stroke. This study explores long-term care trajectories among older men and women with stroke in the Swedish population., Design: Nationwide prospective cohort study., Setting and Participants: All individuals aged ≥70 years hospitalized with a first stroke in 2015-2017 followed in the Swedish population registers for 3 years., Methods: Care trajectories among patients with strokes were visualized and compared to trajectories in 2 control groups: (1) same-aged peers randomly drawn from the general population and (2) older adults with health and sociodemographic characteristics similar to patients with strokes but without stroke identified through propensity score matching. Multivariable Cox regression and multistate models were used to identify determinants of mortality and care trajectories among patients with strokes., Results: We identified 31,560 individuals with stroke (mean age 82.9 years). Already before the stroke, these individuals had a higher comorbidity burden and received more long-term care than their same-aged peers. Compared with both control groups, patients with strokes were also more likely to enter long-term care. However, 38% of patients with strokes survived for 3 years without taking up long-term care. Sex, income, cohabitation, and comorbidities were associated with care trajectories. Care status was a more robust predictor of mortality after stroke than the established Charlson comorbidity index., Conclusions and Implications: Experiencing a stroke increases both mortality and long-term care utilization, and once formal long-term care is provided, exceedingly few patients with strokes return to living without care. However, a considerable part of care utilization and mortality after stroke is concentrated among those with preexisting care needs. Prestroke care utilization should thus be considered in future studies exploring stroke prognosis., Competing Interests: Disclosure The authors declare no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The aim of the study was to investigate the expression of EGFR and HER-2 oncogenes using an experimental two stage chemically induced carcinogenesis protocol on the dorsal skin in FVB/N mice. Forty female FVB/N mice 4 weeks old, were grouped into one control (n = 8) and two experimental groups (Group A: n = 16, Group B: n = 16) following a randomization process. Two-stage carcinogenesis protocol, was implicated, including an initial treatment with 97.4 nmol DMBA on their shaved dorsal skin and subsequent treatments of 32.4 nmol TPA applications after 13 weeks for Group A and after 20 weeks for Group B. The control group C, received no treatment. Skin was examined weekly for tumor development. Post-experiment, animals were euthanized for tissue analysis. The histological status of the skin lesions in the experimental groups corresponded well with tumour advancement (from dysplasia to poorly-differentiated carcinoma). Tumour sections were evaluated histologically and immunohistochemically. EGFR expression was found significantly higher in precancerous and malignant tumours (p = 042 and p = 008 respectively), while tended to be higher in benign tumours (p = 079), compared to normal histology. Moreover, mean percentage of EGFR positive expression in malignant tumours was significantly higher than in benign tumours (p < 001). HER-2 expression was found significantly higher in precancerous and malignant tumours (p = 042 and p = 015 respectively), while tended to be higher in benign tumours (p = 085), compared to normal histology. Furthermore, mean percentage of HER-2 positive expression in malignant tumours was significantly higher than in benign tumours (p = 005). The study demonstrated that in FVB/N mice subjected to a two-stage chemically induced carcinogenesis protocol, there was a significant increase in the expression of EGFR and HER-2 oncogenes in precancerous and malignant skin lesions compared to normal tissue. This suggests a potentially early role of these oncogenes in the progression of skin tumours in this model., Competing Interests: Declaration of competing interest The authors report no competing interests regarding this study., (Copyright © 2024 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Effects on the growth and reproduction of birds are important endpoints in the environmental risk assessment (ERA) of pesticides. Toxicokinetic-toxicodynamic models based on dynamic energy budget theory (DEB) are promising tools to predict these effects mechanistically and make extrapolations relevant to ERA. However, before DEB-TKTD models are accepted as part of ERA for birds, ecotoxicological case studies are required so that stakeholders can assess their capabilities. We present such a case-study, modelling the effects of the fluopyram metabolite benzamide on the northern bobwhite quail (Colinus virginianus). We parametrised a DEB-TKTD model for the embryo stage on the basis of an egg injection study, designed to provide data for model development. We found that information on various endpoints, such as survival, growth, and yolk utilisation were needed to clearly distinguish between the performance of model variants with different TKTD assumptions. The calibration data were best explained when it was assumed that chemical uptake occurs via the yolk and that benzamide places stress on energy assimilation and mobilisation. To be able to bridge from the in vitro tests to real-life exposure, we developed a physiologically-based toxicokinetic (PBK) model for the quail and used it to predict benzamide exposure inside the eggs based on dietary exposure in a standard reproductive toxicity study. We then combined the standard DEB model with the TKTD module calibrated to the egg injection studies and used it to predict effects on hatchling and 14-day chick weight based on the exposure predicted by the PBK model. Observed weight reductions, relative to controls, were accurately predicted. Thus, we demonstrate that DEB-TKTD models, in combination with suitable experimental data and, if necessary, with an exposure model, can be used in bird ERA to predict chemical effects on reproduction., Competing Interests: Declaration of competing interest A. Gergs, M. Ebeling and D. Heckmann are employees of Bayer AG. The work of the other co-authors on the project was funded by Bayer AG. Bayer AG is a manufacturer of the active substance fluopyram investigated in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Understanding the frequency of non-additive effects of pesticides (synergism and antagonism) is important in the context of risk assessment. The goal of this study was to investigate the prevalence of non-additive effects of pesticides to honey bees (Apis mellifera). We investigated a large set of mixtures including insecticides and fungicides of different chemical modes of action and classes. The mixtures included represent a relevant sample of pesticides that are currently used globally. We investigated whether the experimental toxicity of the mixtures could be predicted based on the Concentration Addition (CA) model for acute contact and oral adult bee toxicity tests. We measured the degree of deviation from the additivity predictions of the experimental toxicity based on the well-known Mixture Deviation Ratio (MDR). Further, we investigated the appropriate MDR thresholds that should be used for the identification of non-additive effects based on acceptable rates for false positive (alpha) and true positive (beta) findings. We found that a deviation factor of MDR = 5 is a sound reference for labeling potential non-additive effects in acute adult bee experimental designs when assuming a typical Coefficient of Variation (CV%) = 100 in the determination of the LD 50 of a pesticide (a factor of 2× deviation in the LD 50 resulting from inter-experimental variability). We found that only 2.4 % and 9 % of the mixtures evaluated had an MDR > 5 and MDR < 0.2, respectively. The frequency and magnitude of deviation from additivity found for bees in this study are consistent with those of other terrestrial and aquatic taxa. Our findings suggest that additivity is a good baseline for predicting the toxicity of pesticide mixtures to bees, and that the rare cases of synergy of pesticide mixtures to bees are not random but have a mechanistic basis., Competing Interests: Declaration of competing interest The authors are employees of Bayer Crop Science, a manufacturer of crop protection products., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Unintentional environmental mixtures happen when multiple chemicals co-occur in the environment. A generic mixture assessment factor (MAF), has been proposed to account for this. The MAF is a number by which safe exposure levels for single chemicals are divided to ensure protection against combined exposures to multiple chemicals. Two key elements to judge the appropriateness of a generic MAF are (1) defining the scope of mixtures that need to be addressed by a MAF (i.e.: simple mixtures vs complex mixtures), and (2) the existence of common risk drivers across large spatial scales. Simple mixtures with one to three risk drivers can easily be addressed by chemical-by-chemical regulatory action. Our work provides evidence on the prevalence and complexity of cumulative risk in EU freshwaters based on chemical monitoring data from one of the largest databases in the EU. With 334 chemicals being monitored, low complexity mixtures (one to 3 three risk drivers) dominated. After excluding metals, only 15 out of 307 chemicals (5 %) were most frequent chemical risk drivers. When these 15 chemicals were excluded from the analysis, 95 % of all monitoring site - year combinations did not pose a concern for cumulative risk. Most of these 15 chemicals are already banned or listed in various priority lists, showing that current regulatory frameworks were effective in identifying drivers of single chemical and cumulative risk. Although the monitoring data do not represent the entirety of environmental mixtures in the EU, the observed patterns of (1) limited prevalence of truly complex mixtures, and (2) limited number of overall risk drivers, argue against the need for implementing a generic MAF as a regulatory tool to address risk from unintentional mixtures in EU freshwaters., Competing Interests: Declaration of competing interest Ismael Rodea-Palomares, Zhenglei Gao, Arnd Weyers & Markus Ebeling are employees of Bayer, a manufacturer of pesticides and pharmaceutical products., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: Population aging - which tends to be more pronounced in rural than in urban areas - poses important challenges for facilitating equal opportunities for aging well and 'aging in place.' Unmet health care needs among the older rural population may result in poorer health and higher mortality, but the scientific evidence of a systematic rural mortality disadvantage at older ages is scarce. We argue that systematic urban-rural mortality differences by age may be found if the confounding effect of life expectancy is considered., Study Design: Nationwide population-based study., Methods: We draw on age- and sex-specific data for the population aged 60+ years in NUTS-3 regions in Germany (2016-2018) and LAU-1 regions in England & Wales (2017-2019). To account for the confounding effect of life expectancy, we compare age-specific mortality only across urban and rural regions with similar life expectancy levels. We quantify statistical uncertainty with bootstrapping., Results: The results show a remarkable shift from higher mortality in urban regions to higher mortality in rural regions with increasing age, when controlling for the confounding effect of life expectancy. That is, the urban mortality disadvantage is strongest for the population aged 60-79 years, whereas the pattern shifts toward a rural mortality disadvantage for the population aged 80 years and older. This pattern is present at all levels of life expectancy, for both sexes and in both countries., Conclusion: The shift from urban to rural excess mortality over age suggests that regions may vary in their capability to respond to arising health issues across older ages. This systematic mortality disadvantage is of high public health relevance and should be considered in designing policies to reduce regional mortality disparities., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Targeting RNA drastically expands our target space to therapeutically modulate numerous cellular processes implicated in human diseases. Of particular interest, drugging pre-mRNA splicing appears a very viable strategy; to control levels of splicing product by promoting the inclusion or exclusion of exons. After describing the concept of "splicing modulation", this chapter will cover the outstanding progress achieved in this field, by highlighting the breakthrough accomplished recently for the treatment of spinal muscular atrophy using two therapeutic modalities: splice switching oligonucleotides and small molecules. This review discusses the vital but feasible requirement for such drugs to deliver selectivity, and critical safety aspects are highlighted. Transformational medicines such as those developed to treat SMA are likely just the beginning of this story., (© 2019 Elsevier B.V. All rights reserved.)

Objective: Look-alike, sound-alike (LASA) drug name substitution errors in children may pose potentially severe consequences. Our objective was to determine the degree of potential harm pediatricians ascribe to specific ambulatory LASA drug substitution errors., Methods: We developed a unified list of LASA pairs from published sources, removing selected drugs on the basis of preparation type (eg, injectable drugs). Using a modified Delphi method over 3 rounds, 38 practicing pediatricians estimated degree of potential harm that might occur should a patient receive the delivered drug in error and the degree of potential harm that might occur from not receiving the intended drug., Results: We identified 3550 published LASA drug pairs. A total of 1834 pairs were retained for the Delphi surveys, and 608 drug pairs were retained for round 3. Final scoring demonstrated that participants were able to identify pairs where the substitutions represented high risk of harm for receiving the delivered drug in error (eg, did not receive methylphenidate/received methadone), high risk of harm for not receiving the intended drug (eg, did not receive furosemide/received fosinopril), and pairs where the potential harm was high from not receiving the intended drug and from erroneously receiving the delivered drug (eg, did not receive albuterol/received labetalol)., Conclusions: Pediatricians have identified LASA drug substitutions that pose a high potential risk of harm to children. These results will allow future efforts to prioritize pediatric LASA errors that can be screened prospectively in outpatient pharmacies., (Copyright © 2016 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Object: To evaluate the introduction of intraoperative and postoperative pneumatic compression additionally to the use of compression stockings, low molecular weight heparin-LMWH and early mobilization, a retrospective study in cranial neurosurgery using intraoperative MRI was performed., Methods: A retrospective analysis of 207 neurosurgical patients using intraoperative MRI was performed. A group of 86 patients was treated with the additional use of intraoperative and postoperative pneumatic compression until mobilization out of bed. One hundred twenty-one patients were treated without the use of additional pneumatic compression. Postoperatively the patients were screened for deep venous thrombosis by ultrasound and pulmonary embolism by CT-scan if suspicious. Statistical analysis was performed., Results: The development of deep venous thrombosis was reduced from 9.9% to 3.5% in our patients with the additional use of intraoperative and postoperative pneumatic compression. That is a 64.6% relative risk reduction to develop deep venous thrombosis with the use of intraoperative and postoperative pneumatic compression. An additional 52% relative risk reduction was found for the chance of developing pulmonary embolism. In the 15 patients with detected deep venous thrombosis, the OR-time was more than 100 min longer than in the 192 patients without detected deep venous thrombosis. The difference between both groups was significant., Conclusion: This study demonstrates the benefit of pneumatic compression with a risk reduction for the development of thromboembolic complications. OR-time is another risk factor that attributes to a significant risk for the development of thromboembolic complications., (Copyright © 2015 Elsevier B.V. All rights reserved.)

It is claimed that apoA-I expression is repressed in mice by cholic acid (CA) and its taurine conjugate, taurocholic acid (TCA) via farnesoid X receptor (FXR) activation. We measured apoA-I expression in mice, hamsters, and rats treated with highly potent and selective synthetic FXR agonists or with TCA. All of the synthetic agonists bound to FXR with high affinity in a scintillation proximity assay. However, TCA did not compete with the radioligand up to the highest concentration used (100 μM). The C-site regulatory region of apoA-I, through which FXR has been reported to regulate its expression, is completely conserved across the species investigated. In both male and female human apoA-I-transgenic mice, we reproduced the previously reported strong inhibition of human apoA-I expression upon treatment with the typical supraphysiological dose of TCA used in such studies. However, in contrast to some previous reports, TCA did not repress murine apoA-I expression in the same mice. Also, more-potent and -selective FXR agonists did not affect human or murine apoA-I expression in this model. In LDL receptor-deficient mice and Golden Syrian hamsters, selective FXR agonists did not affect apoA-I expression, whereas in Wistar rats, some even increased apoA-I expression. In conclusion, selective FXR agonists do not repress apoA-I expression in rodents. Repression of human apoA-I expression by TCA in transgenic mice is probably mediated through FXR-independent mechanisms.

Objective: The aim of this study was to pilot test a screening approach to detect potential look-alike, sound-alike (LASA) errors in pediatric outpatient prescriptions., Method: Medicaid pharmacy claims from one state were reviewed. From a list of LASA drug pairs, we identified candidate pairs meeting the following criteria: 1) one drug was commonly prescribed in children; 2) the paired drug was uncommonly prescribed for children; and 3) both drugs were available as oral preparations only, resulting in 11 LASA pairs. We identified patients who usually received one drug in a pair, then presented with a first dispensing of the paired drug, representing a "screening alert" for potential LASA error. We determined a "true error" as any patient who triggered a screening alert, received only one dispensing of the paired drug in the subsequent 6 months, and had no diagnoses supporting the dispensing of the paired drug., Results: Among the 22 test drugs, there were 1 420 091 prescriptions to 173 005 subjects. There were 395 screening alerts generated, representing a screening alert frequency of 0.28 screening alerts per 1000 prescriptions. We identified 43 true LASA errors. In the dataset, the overall LASA error rate is estimated to be approximately 0.00003%, or 0.03 LASA errors per 1000 prescriptions., Conclusion: Prescription dispensing patterns can be used to screen for LASA errors in pediatric prescriptions. The rates of pediatric LASA errors appear to be much lower than other types of pediatric medication errors and may be best addressed by automated processes., (2010 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Objective: The purpose of this study was to describe the success rate of and analyze differences in neonatal outcomes with labor induction, compared with elective cesarean delivery in women with early-onset severe preeclampsia., Study Design: We conducted a cross-sectional study of women with severe preeclampsia who required delivery between 24 and 34 weeks of gestation. Bivariate and multivariable regression analyses were used to determine factors that were associated with assignment to, success of, and odds of neonatal outcomes after induction of labor., Results: Fifty-seven and four-tenths percent of 491 women underwent induction of labor. Vaginal delivery occurred in 6.7%, 47.5%, and 68.8% of women who underwent labor induction between 24 and 28, 28 and 32, and 32 and 34 weeks of gestation, respectively. Induction of labor was not associated with an increase in neonatal morbidity or mortality rate after we controlled for gestational age and other confounders., Conclusion: Neonatal outcomes are not worsened by induction of labor in women with early-onset severe preeclampsia, although it is rarely successful at <28 weeks of gestation.

Background: Spontaneous pneumothorax is a complication that is commonly reported in patients with cystic fibrosis (CF). An understanding of the pathophysiology of this complication and its consequences is important for the management of patients with CF., Objective: To identify risk factors associated with pneumothorax and to determine the prognosis of CF patients following an episode of pneumothorax., Design: A retrospective observational cohort study of the National Cystic Fibrosis Patient Registry between the years 1990 and 1999., Patients: The registry contained data on 28,858 patients with CF who had been followed up over those 10 years at CF centers across the United States., Results: Pneumothorax occurred with an average annual incidence of 0.64% and in 3.4% of patients overall. There was no increased occurrence by sex, but CF was more prevalent in older patients (mean [+/- SD] age, 21.9 +/- 9.1 years) with more severe pulmonary impairment (nearly 75% of patients with FEV1 of < 40% predicted). The principal risks associated with an increased occurrence of pneumothorax included the presence of Pseudomonas aeruginosa (odds ratio [OR], 2.3), Burkholderia cepacia (OR, 1.8), or Aspergillus (OR, 1.3) in sputum cultures, FEV1 < 30% predicted (OR, 1.5), enteral feeding (OR, 1.7), Medicaid insurance (OR, 1.1), pancreatic insufficiency (OR, 1.4), allergic bronchopulmonary aspergillosis (OR, 1.5), and massive hemoptysis (OR, 1.4). There is an increased morbidity (eg, increased number of hospitalizations and number of days spent in the hospital) and an increased 2-year mortality rate following pneumothorax., Conclusion: Pneumothorax is a serious complication in CF patients, occurring more commonly in older patients with more advanced lung disease. Nearly 1 in 167 patients will experience this complication each year. There is an attributable mortality to the complication and considerable morbidity, resulting in increased health-care utilization and a measurable decline in lung function.

Background: Massive hemoptysis is a complication commonly reported in patients with cystic fibrosis (CF). An understanding of the pathophysiology of this complication and its consequences is important for the management of patients with CF., Objectives: To identify risk factors associated with massive hemoptysis, and to determine the prognosis of patients following an episode of massive hemoptysis., Design: A retrospective, observational cohort study of the National CF Patient Registry between the years 1990 to 1999., Patients: The Registry contained data on 28,858 patients with CF observed over 10 years at CF centers across the United States., Results: Massive hemoptysis occurred with an average annual incidence of 0.87% and in 4.1% of patients overall. There was no increased occurrence by sex, but it was more prevalent in older patients (mean age, 24.2 +/- 8.7 years [+/- SD]) with more severe pulmonary impairment (nearly 60% of patients who had an episode of massive hemoptysis had FEV1 < 40% predicted). The principal risks associated with an increased occurrence of massive hemoptysis included the presence of Staphylococcus aureus in sputum cultures (odds ratio [OR], 1.3) and diabetes (OR, 1.1). There was an increased morbidity (eg, increased hospitalizations and hospital days) and an increased 2-year mortality following massive hemoptysis., Conclusion: Massive hemoptysis is a serious complication in CF patients, occurring more commonly in older patients with more advanced lung disease. Nearly 1 in 100 patients will have this complication each year. There is an attributable mortality to the complication and considerable morbidity, resulting in increased health-care utilization and a measurable decline in lung function.

Objective: The object of this study was to compare neonatal outcomes of term uncomplicated pregnancies delivered by scheduled repeat cesarean with outcomes of babies born to mothers intending to deliver vaginally., Study Design: This retrospective cohort study describes neonatal outcomes of term uncomplicated pregnancies. Neonates of mothers intending to deliver vaginally (n = 3134) are compared with neonates born by elective repeat cesarean delivery prior to labor (n = 117)., Results: Neonates born by elective repeat cesarean are more frequently admitted to advanced care nurseries than infants born to mothers intending to deliver vaginally (risk ratio 3.58, 95% confidence interval 3.35-3.58)., Conclusion: The decision to undergo scheduled cesarean delivery appears to negatively impact immediate neonatal outcomes.

Objective: The purpose of this study was to determine whether hyaline membrane disease is increased in newborn infants who are born to women with preeclampsia compared with control subjects., Study Design: This was a historic cohort study of deliveries between 24 and 37 weeks of gestation at the Medical University of South Carolina from 1996 through 2002. Singleton infants who were born to women with preeclampsia were compared with nonpreeclamptic control subjects. The incidence of hyaline membrane disease was compared by chi 2 analysis and Fisher exact test, with significance at a probability value of <.05. Logistic regression analysis was performed to address potential confounders., Results: There were 814 women with preeclampsia and 3021 control subjects. When we controlled for confounding factors, there was a significant increase in the incidence of hyaline membrane disease in the preeclamptic group overall (odds ratio, 1.35; 95% CI, 1.03-1.78). The risk was more pronounced in neonates who were born at 32 weeks of gestation (odds ratio, 1.93; 95% CI, 1.28-2.91)., Conclusion: The risk of hyaline membrane disease in neonates at < 32 weeks of gestation is increased in patients with preeclampsia. This supports the contention that fetal lung maturity is not accelerated in preeclampsia.

Interleukin-10 is an important anti-inflammatory and immunosuppressive cytokine with major impact on several immune reactions, including regulatory mechanisms in the skin. Recently, we performed a phase II trial in psoriatic patients receiving subcutaneously interleukin-10 over 7 wk. The clinical response suggested that interleukin-10 might represent a novel anti-psoriatic drug. In order to understand better the mode of action and to elucidate the effects of systemic interleukin-10 treatment on the skin immune system, skin punch biopsies from sites different from interleukin-10 injection were analyzed. Biopsies were obtained from the patients before, at the end, and 3 wk after interleukin-10 therapy. The results are reported here. Histologic examination showed a decrease of several parameters reflecting the psoriatic disease activity as acanthosis and extension of the horny layer. Immunohistologic examination demonstrated decreasing numbers of infiltrating T cells, dermal CD1a+ cells, and a diminished proliferation of epidermal cells. Using a novel, quantitative reverse transcriptase-polymerase chain reaction approach a significant shift within the cytokine pattern was found. Interleukin-10 therapy led to a decrease of cutaneous interleukin-8 and interleukin-10 mRNA expression. Whereas no significant changes of interleukin-6, tumor necrosis factor-alpha, and interferon-gamma expression were found, interleukin-4 was strongly upregulated suggesting a shift from a type 1 towards a type 2 cytokine pattern. The changes within the local cytokine pattern seem to be disease-related, as an inverse course was found in a single interleukin-10 nonresponding patient. Our findings demonstrate considerable effects of systemic interleukin-10 application on the skin immune systems, which might contribute to the anti-psoriatic activity of interleukin-10.

Objective: The aim of the study was to describe risk factors for neonatal death among twins born in South Carolina., Study Design: South Carolina publicly accessible live birth and infant death cohort files for live-born twins >500 g were reviewed for the years 1988 through 1993. Infants with lethal anomalies were deleted from the cohort before analysis. Risk factors for neonatal death were determined for the entire cohort and for the birth weight categories of 500 to 999 g, 1000 to 1499 g, 1500 to 2499 g, and >/=2500 g. Statistical comparisons were performed with the Mantel-Haenszel chi2 test and multivariate logistic regression., Results: Of 7833 live-born twins, 263 (3.4%) died during the neonatal period. The mean birth weight was 2357 +/- 650 g (range 500-5358 g) at a mean gestational age of 35.7 +/- 3.5 weeks. Overall neonatal mortality rates were significantly increased (P <.001) for twins whose mothers were nonwhite (4.2 vs 2.8%), were <20 years old (6.0 vs 3.2%), or received no prenatal care (14.7 vs 3.1%). After we controlled for population characteristics with multivariate techniques, analysis revealed birth weight <2500 g and residence in the most populous urban areas to be associated with increased neonatal mortality rates. After stratification into birth weight categories, race was no longer a significant variable; in fact, nonwhite twins had a survival advantage at birth weights <1500 g, but this was not significant. Maternal age <20 years was associated with a higher neonatal mortality rate for infants with birth weights between 1500 and 2499 g. Absence of prenatal care significantly increased the neonatal mortality rate for twins >/=1500 g but not for those who were smaller. For infants weighing 500 to 999 g neonatal mortality rates were significantly lower at hospitals with >/=2000 deliveries/y than at hospitals with lower delivery volumes (P =.005)., Conclusions: Although the overall neonatal mortality rate for twins continues to improve, increased rates are still seen among blacks, teenagers, and women who receive no prenatal care. Twins between 500 and 999 g have significantly reduced neonatal mortality rates when delivered at hospitals with a high obstetric volume.

Objective: Our purpose was to determine whether preterm birth of twins is associated with an increased risk of preterm birth in a subsequent singleton pregnancy., Study Design: The Medical University of South Carolina perinatal database was accessed to identify a cohort of patients who were delivered of twins followed by a singleton gestation (1981 to 1993). Maternal transports were excluded to minimize referral bias. Preterm birth was defined as < 37 weeks' gestation. Relative risks with 95% confidence intervals were calculated., Results: One hundred forty-four patients were identified who were delivered of twins followed by a singleton gestation. Preterm delivery occurred in 86 (59.7%) of the twins and 21 (14.6%) of the subsequent singletons. Preterm birth of twins was associated with a significantly increased risk of preterm delivery in a subsequent singleton pregnancy (relative risk 2.87, 95% confidence interval 1.02 to 8.09). In the subset of women who were delivered of twins at < 30 weeks' gestation, 42% of the subsequent singletons were delivered preterm (relative risk 6.11, 95% confidence interval 2.07 to 18.02). The relative risk of preterm birth of a singleton after delivery of twins between 30 and 34 weeks' gestation was 3.63 (95% confidence interval 1.02 to 12.92). However, if the preceding twins delivered between 34 and 37 weeks' gestation, the relative risk of preterm birth of the subsequent singleton was not significantly increased (relative risk 1.42, 95% confidence interval 0.40 to 5.01)., Conclusions: Preterm birth of twins before 34 weeks' gestation is associated with a significant risk for preterm delivery in a subsequent singleton pregnancy. The magnitude of risk increases with decreasing gestational age of the preceding twin delivery.