Neonatal screening for congenital adrenal hyperplasia in North-Eastern Italy: a report three years into the program

AIMS: To evaluate the incidence of congenital adrenal hyperplasia (CAH) in the Northern Italian population and the efficiency of the North-Eastern Italy screening program. To adjust cut-off levels for 17-hydroxyprogesterone (17-OHP) in relation to gestational age and birth weight, comparing the benefits in terms of reduction of recall rates with the two approaches and ultimately choosing the better of the two. SUBJECTS AND METHODS: Since September 2001, blood samples from neonates born in North-Eastern Italy have been screened with a fluoroimmunoassay method for 17-OHP determination (DELFIA). A preliminary cut-off level of > or = 30 nmol/l was set both for term and preterm newborns. The values of 17-OHP were analysed using statistical methods in relation to gestational age and birth weight in order to modify the cut-off on the basis of our data. RESULTS: After 33 months of screening we screened 128,282 newborns and detected 6 affected babies. During the first 8 months of screening among the recalled babies, 89.6 and 78.1% were preterm and low-birth-weight newborns, respectively, with a recall rate of 2.59% for premature neonates and of 4.94% for babies with birth weights < 2,500 g. We chose a new cut-off value of 50 nmol/l for preterm newborns only and, after 4 months, the recall rate was reduced to 0.83% for these infants and to 1.83% for low-birth-weight infants. CONCLUSION: After 33 months of screening for CAH in North-Eastern Italy, we report an incidence of 1:21,380. In 5 out of 6 affected babies, the diagnosis was established only after a positive screening test, which prevented a severe salt-wasting crisis in these babies. The cut-off level related to gestational age led to a significant reduction in the number of false-positives among preterm babies.We therefore intend to continue with the screening program for CAH in North-Eastern Italy, keeping a gestational-age-related cut-off in the hope that our data may encourage a national screening program for CAH.     

Functional abilities at age 4 years of children born before 29 weeks of gestation.

OBJECTIVES--To assess the rate of impairment and disability among babies born very preterm and to investigate the association between such impairment and gestational age at birth. DESIGN--Cohort study of a geographically defined population of babies. SETTING--Oxford Regional Health Authority. SUBJECTS--All babies born alive before 29 weeks of gestation to mothers resident in the region during 1984-6. MAIN OUTCOME MEASURES--Survival rates and rates of impairment and disability among survivors at the age of 4 years. RESULTS--Of the 342 babies, half (170) survived to be discharged home. Of the 164 survivors to age 4 years, 153 (93%) were assessed. A total of 35 (23%; 95% confidence interval 16% to 30%) were severely disabled and only 54 (35%; 28% to 43%) were unimpaired. The risk of impairment and disability increased with decreasing gestational age at birth (p < 0.003). CONCLUSIONS--With the increasing survival rate among babies born before 29 weeks of gestation, we need urgently to establish reliable ways of monitoring the proportion of survivors who have a disability.     

Dual Processing Model for Medical Decision-Making: An Extension to Diagnostic Testing

Dual Processing Theories (DPT) assume that human cognition is governed by two distinct types of processes typically referred to as type 1 (intuitive) and type 2 (deliberative). Based on DPT we have derived a Dual Processing Model (DPM) to describe and explain therapeutic medical decision-making. The DPM model indicates that doctors decide to treat when treatment benefits outweigh its harms, which occurs when the probability of the disease is greater than the so called “threshold probability” at which treatment benefits are equal to treatment harms. Here we extend our work to include a wider class of decision problems that involve diagnostic testing. We illustrate applicability of the proposed model in a typical clinical scenario considering the management of a patient with prostate cancer. To that end, we calculate and compare two types of decision-thresholds: one that adheres to expected utility theory (EUT) and the second according to DPM. Our results showed that the decisions to administer a diagnostic test could be better explained using the DPM threshold. This is because such decisions depend on objective evidence of test/treatment benefits and harms as well as type 1 cognition of benefits and harms, which are not considered under EUT. Given that type 1 processes are unique to each decision-maker, this means that the DPM threshold will vary among different individuals. We also showed that when type 1 processes exclusively dominate decisions, ordering a diagnostic test does not affect a decision; the decision is based on the assessment of benefits and harms of treatment. These findings could explain variations in the treatment and diagnostic patterns documented in today’s clinical practice.     

Los suplementos de calcio y el posible aumento del riesgo cardiovascular

The primary goal of osteoporosis treatment is to prevent the occurrence of fragility fractures, and thereby reduce morbidity and mortality. Among the various approaches to the treatment of this disease include ensuring proper calcium intake and to obtain adequate levels of vitamin D. Virtually all clinical trials with drugs used to treat osteoporosis systematically include calcium and vitamin D supplements. In light of the recent publication of clinical trials and meta-analyses, a possible increase in cardiovascular risk, particularly in the form of a myocrdial infarction, is hypothesised in patients taking calcium supplements. However, data published to date are inconclusive. Until the development of new scientific evidence, it seems reasonable to recommend, whenever practicable and individualized for each patient, increasing calcium intake with food and reserve supplements for patients with very low calcium intake in the diet. It would also be advisable for the administration of total daily dose to be fractionated throughout the day and with meals, and to obtain appropriate levels of vitamin D (25-hydroxycholecalciferol or calcidiol), along with the basic treatment for osteoporosis that is decided to be prescribed to patients.     

78例胎盘早剥临床分析

目的：探讨胎盘早剥的诱发因素、手术方式和临床处理方法。方法：采用回顾性病例分析的方法,对2010年6月至2012年1月在我院妇产科接受治疗的78例胎盘早剥患者的临床资料进行统计,分析胎盘早剥的诱因、临床分度及处置原则。结果：诱发因素：妊娠期高血压病占第1位,胎膜早破为第2位,妊娠期合并糖尿病为第3位。此外,羊水过多、妊娠合并子宫肌瘤、外伤等也是引起胎盘早剥的因素。在78例胎盘早剥患者中,重度的有18例,中度的有32例,这50例患者全用采取剖宫产进行处置。另有28例为轻度胎盘早剥,其中6例采用阴道分娩。结论：胎盘早剥以妊娠期高血压、胎膜早破、妊娠期糖尿病为主要发病诱因,中重度胎盘早剥一般用剖宫产终止妊娠,轻度胎盘早剥可部分用阴道分娩。     

Refractive Status at Birth: Its Relation to Newborn Physical Parameters at Birth and Gestational Age

Background

Refractive status at birth is related to gestational age. Preterm babies have myopia which decreases as gestational age increases and term babies are known to be hypermetropic. This study looked at the correlation of refractive status with birth weight in term and preterm babies, and with physical indicators of intra-uterine growth such as the head circumference and length of the baby at birth.

Methods

All babies delivered at St. Stephens Hospital and admitted in the nursery were eligible for the study. Refraction was performed within the first week of life. 0.8% tropicamide with 0.5% phenylephrine was used to achieve cycloplegia and paralysis of accommodation. 599 newborn babies participated in the study. Data pertaining to the right eye is utilized for all the analyses except that for anisometropia where the two eyes were compared. Growth parameters were measured soon after birth. Simple linear regression analysis was performed to see the association of refractive status, (mean spherical equivalent (MSE), astigmatism and anisometropia) with each of the study variables, namely gestation, length, weight and head circumference. Subsequently, multiple linear regression was carried out to identify the independent predictors for each of the outcome parameters.

Results

Simple linear regression showed a significant relation between all 4 study variables and refractive error but in multiple regression only gestational age and weight were related to refractive error. The partial correlation of weight with MSE adjusted for gestation was 0.28 and that of gestation with MSE adjusted for weight was 0.10. Birth weight had a higher correlation to MSE than gestational age.

Conclusion

This is the first study to look at refractive error against all these growth parameters, in preterm and term babies at birth. It would appear from this study that birth weight rather than gestation should be used as criteria for screening for refractive error, especially in developing countries where the incidence of intrauterine malnutrition is higher.     

The role of degradation of fetal haemoglobin in the energy supply of very low body weight pre-term babies

Low body weight premature babies born before the 32nd gestational week were studied to analyse the postnatal fall in plasma haemoglobin and in quantitative changes in amino acid levels. Red blood cells of premature low body weight infants were found to disintegrate more rapidly than those of mature newborns. Thin-layer ion-exchange chromatographic studies showed that amino acids originating from the degrading haemoglobin-F lead to rise in plasma amino acids. These amino acids might play a role as substrates for gluconeogenesis in the energy supply of low body weight premature babies during the special fasting state just after birth.     

301例早产儿视网膜病变筛查结果及其高危因素分析

目的:调查早产儿视网膜病变(ROP)的发生情况并分析其高危因素。方法:选取2017年6月至2018年6月在我院进行眼底检查的301例早产儿,依据《早产儿治疗用氧和视网膜病变防治指南》和《中国早产儿视网膜病变筛查指南》对早产儿进行筛查和随诊,同时收集早产儿及其母亲的相应病历信息,采用多因素Logistic回归分析分析ROP的高危因素。结果:301例早产儿中,共检出ROP患儿43例,其中须接受治疗的患儿13例,所有患儿经过2-6个月的治疗和随诊后均好转。围产因素中,胎龄小、出生体重低、吸氧、输血、有急性呼吸窘迫综合征(ARDS)的早产儿ROP检出率更高(均P0.05);母体因素中,多胎分娩的早产儿ROP检出率高于单胎分娩的早产儿(P0.05)。Logistic回归分析显示,胎龄小、出生体重低、吸氧、输血和有ARDS为早产儿ROP的高危因素(P0.05)。结论:早产儿ROP发病率较高,胎龄小、出生体重低、吸氧、输血和有ARDS是其高危因素,在临床实践中应给予重视,及早发现ROP并规范治疗,以降低早产儿ROP的发病率。     

Futility and the obligations of physicians

It is becoming increasingly common (at least in the United States) for doctors to appeal to futility judgments as the basis for certain types of clinical decisions, such as the decision to withhold CPR. The clinical use of futility judgments raises two basic questions regarding futility. First, how is the concept of futility to be understood? Secondly, once we have a clearer understanding of futility, what role should determinations of futility play in clinical decision-making? Much of the discussion about the concept of futility has centered on the value-ladenness of futility judgments. I argue that futility determinations need to be distinguished from two other types of value-based judgments, namely, identification of the goals of treatment and treatment decisions based on an assessment of the benefits and burdens of treatment. If this distinction is sound, it suggests a very limited role for futility determinations in clinical decisionmaking, a role which should serve to promote communication between doctor and patient.     

Twin pregnancy with complete hydatidiform mole and coexisting fetus following ovulation induction with a non-prescribed clomiphene citrate regimen: a case report

Introduction

Until now, studies on paracetamol given intravenously have mainly been performed with the pro-drug propacetamol or with paracetamol in preterm babies above 32 weeks of gestation. Studies in these babies indicate that intravenous paracetamol is tolerated well, however studies on the efficacy of intravenous paracetamol are lacking. There are no pharmacokinetic data on the administration of multiple doses of paracetamol in preterm babies with a gestational age below 32 weeks.

Case presentation

We present a case series of nine Caucasian preterm babies, six boys and three girls, with a mean gestational age of 28.6 weeks (range 25.9 to 31.6 weeks). Case one, a girl with a gestational age of 25 weeks and six days, presented with necrotizing enterocolitis. In the second case, a female baby with a gestational age of 26 weeks and two days presented with hematoma. In case three, a female baby with a gestation of 26 weeks and one day developed intraventricular hemorrhage. In case four, a male baby with a gestational age of 31 weeks and four days presented with pain after vacuum delivery. Case five, a female baby born after a gestation of 29 weeks and six days presented with hematoma. In case six, a male baby with a gestation of 30 weeks and six days presented with hematoma. In case seven, a male baby, born with a gestational age of 30 weeks and six days, presented with caput succedaneum and hematoma. In case eight, a male baby, born after a gestation of 28 weeks and four days, developed abdominal distention. Case nine, a female baby, born with a gestational age of 27 weeks and three days presented with hematoma. These babies were treated with intravenous paracetamol 15 mg/kg every six hours. Serum concentrations and aspartate transaminase were determined after prolonged administration. Pain scores were assessed using the Premature Infant Pain Profile.

Conclusion

Paracetamol serum concentrations ranged from 8 to 64 mg/L after eight to 12 doses of intravenous paracetamol. Adequate analgesia was obtained in seven babies. During paracetamol therapy the median serum level of aspartate transaminase was 20 U/L (range 12 to 186 U/L). This case series indicates that prolonged intravenous administration of paracetamol in preterm babies with a gestational age of less than 32 weeks is tolerated well in the first days after birth. However, in the absence of proper pharmacokinetic data in this age group we cannot advocate the use of paracetamol intravenously.     

Constructing normalcy and discrepancy indexes for birth weight and gestational age using a threshold regression mixture model

Birth weight and gestational age are important measures of a newborn's intrinsic health, serving both as outcome measures and explanatory variables in health studies. The measures are highly correlated but occasionally inconsistent. We anticipate that health researchers and other scientists would be helped by summary indexes of birth weight and gestational age that give more precise indications of whether the birth outcome is healthy or not. We propose a pair of indexes that we refer to as the birth normalcy index or BNI and birth discrepancy index or BDI. Both indexes are simple functions of birth weight and gestational age and in logarithmic form are orthogonal by construction. The BNI gauges whether the birth weight and gestational age combination are in a normal range. The BDI gauges whether birth weight and gestational age are consistent. We present a three-component mixture model for BNI, with the components representing premature, at-risk, and healthy births. The BNI distribution is derived from a stochastic model of fetal development proposed by Whitmore and Su (2007, Lifetime Data Analysis 13, 161-190) and takes the form of a mixture of inverse Gaussian distributions. We present a noncentral t-distribution as a model for BDI. BNI and BDI are also well suited for making comparisons of birth outcomes in different reference populations. A simple z-score and t-score are proposed for such comparisons. The BNI and BDI distributions can be estimated for births in any reference population of interest using threshold regression.     

Where is the Evidence for Assessing Evidence‐Based Restoration? Comments on Ntshotsho et al. (2010)

In their article “Assessing the evidence base for restoration in South Africa,” Ntshotsho et al. attempt to determine whether restoration in South Africa is evidence based by reporting on 10 projects' baseline data collection, goal setting, and monitoring. However, their contribution suffers from two major constraints. First, they confuse assessing the evidence base with assessing whether restoration is evidence based. Truly, assessing the evidence base would entail a systematic review of the quantity and quality of information available as well as the conclusions supported, perhaps in a meta‐analytical framework. Determining if restoration is evidence based would require a survey of project managers to evaluate if they take decisions based on scientific information. Second, Ntshotsho et al. do not clearly distinguish successfully achieving restoration project goals from successfully restoring ecosystems. They largely focus on projects' socioeconomic goals without emphasizing that these goals are, by definition, secondary to ecological goals in determining restoration success. Thus, Ntshotsho et al. provide neither a sound assessment of the evidence base for restoration nor whether restoration is evidence based. To evaluate and encourage evidence‐based restoration in South Africa, we recommend a simple assessment of the basis on which restoration managers make decisions, identification of factors precluding evidence‐based decision‐making, and development of platforms to evaluate the data collected in restoration programs to generate an evidence base from which to make defendable decisions.     

AUTONOMY AND ETHICAL TREATMENT IN DEPRESSION

Antidepressant medication and evidence‐based psychotherapy have largely equivalent efficacy in the management of the common, less severe grades of depression. As a result, several national guidelines recommend that either can be used in the treatment of this disorder. Psychotherapy, however, differs in that it assists insight into how the depressed person appraises and manages the stressors that frequently trigger depressive episodes. I argue that the self‐knowledge achieved through psychotherapy has moral value in that it promotes the autonomy of stressor‐related decisions. I further argue that such an effect comprises a compelling moral reason for doctors to see evidence‐based psychotherapy not as merely optional, but as a necessary treatment for their patients with depression.     

Application of single-cell technology in cancer research

In this review, we have outlined the application of single-cell technology in cancer research. Single-cell technology has made encouraging progress in recent years and now provides the means to detect rare cancer cells such as circulating tumor cells and cancer stem cells. We reveal how this technology has advanced the analysis of intratumor heterogeneity and tumor epigenetics, and guided individualized treatment strategies. The future prospects now are to bring single-cell technology into the clinical arena. We believe that the clinical application of single-cell technology will be beneficial in cancer diagnostics and treatment, and ultimately improve survival in cancer patients.     

Evaluation of transcutaneous bilirubinometry in preterm infants of gestational age 32-34 weeks

Aims: The aim of this prospective study was to evaluate the accuracy of transcutaneous bilirubinometry using the Minolta Air-Shields JM-103 device in preterm newborns of gestational age 32-34 weeks, and to identify the most appropriate measurement site. Methods: Transcutaneous bilirubin (TcB) measurements were performed over forehead, sternum and abdomen, if total serum bilirubin (TSB) had to be determined on clinical indication in neonates of selected gestational age. TSB levels were measured in a clinical laboratory using direct spectrophotometry. In order to assess transcutaneous bilirubinometry accuracy, differences between TSB and TcB, their CI95%, and correlation coefficients (r) between TcB and TSB were evaluated. Results: The study group consisted of 44 infants, including 6 very low birth weight (VLBW) neonates. The correlations between transcutaneous and laboratory values were found to be significant and close. Minimal differences were observed when measured over sternum. The measurements over forehead had a tendency to underestimate TSB levels. Conclusions: Noninvasive measurement by Minolta JM-103 demonstrated significant accuracy. The authors recommend measurements over sternum or abdomen in premature infants born within 32-34 gestational weeks as a reliable and accurate neonatal hyperbilirubinemia screening test. Transcutaneous bilirubinometry has the potential to reduce the number of blood samplings, thus reducing neonatal pain and discomfort, parental distress and medical care cost.     

Birds Do It. Bees Do It. So Why Not Single Women and Lesbians?

Infertile couples have come to take assisted reproductive technologies (ART) for granted. An increasing number of single women and lesbian couples also desire to have children and turn to ART, especially donor insemination, to fulfill this desire. While most married couples find that access to ART is limited primarily by the ability to pay, for single women and lesbian couples, the story may be much different. In the United States, they may find that doctors and infertility clinics view their desires as immoral and refuse to accept them as patients, although other doctors and clinics readily accept them. In most other countries, however, it is against the law for single women and lesbian couples to make use of ART, including donor insemination.
In this paper I will argue that marital status and sexual orientation should not serve as a barrier to accessing the world of reproductive medicine. I will base this conclusion on two arguments. First, that justice requires that we treat like cases alike. Just as we would not accept or reject patients for cardiac rehabilitation programs based on factors such as a history of poor eating habits, so too we should not look at nonmedical factors such as marital status when deciding whether to treat infertility. For the second justification for the conclusion of equal access to ART, I will examine the concept of the family. I will argue that it is morally acceptable for single women and lesbian couples to have children and to head families.     

Birds do it. Bees do it. So why not single women and lesbians?

Infertile couples have come to take assisted reproductive technologies (ART) for granted. An increasing number of single women and lesbian couples also desire to have children and turn to ART, especially donor insemination, to fulfill this desire. While most married couples find that access to ART is limited primarily by the ability to pay, for single women and lesbian couples, the story may be much different. In the United States, they may find that doctors and infertility clinics view their desires as immoral and refuse to accept them as patients, although other doctors and clinics readily accept them. In most other countries, however, it is against the law for single women and lesbian couples to make use of ART, including donor insemination.
In this paper I will argue that marital status and sexual orientation should not serve as a barrier to accessing the world of reproductive medicine. I will base this conclusion on two arguments. First, that justice requires that we treat like cases alike. Just as we would not accept or reject patients for cardiac rehabilitation programs based on factors such as a history of poor eating habits, so too we should not look at nonmedical factors such as marital status when deciding whether to treat infertility. For the second justification for the conclusion of equal access to ART, I will examine the concept of the family. I will argue that it is morally acceptable for single women and lesbian couples to have children and to head families.     

肺表面活性物质救治近足月儿呼吸窘迫综合征的临床疗效观察

目的:观察肺表面活性物质在近足月儿呼吸窘迫综合征救治中的作用。方法:按照家属自愿的原则将41例确诊为新生儿呼吸窘迫综合征且胎龄介于34周-36周之间的近足月儿分为治疗组及对照组,治疗组23例,对照组18例,比较两组患儿血气分析结果、呼吸机参数、气管插管率、上机时间、存活率及住院时间。结果:治疗组患儿,用药后无论临床表现还是胸片均有不同程度的改善。用药后6小时,治疗组PaO2及PaCO2均优于对照组(P<0.05);比较两组中机械通气患儿呼吸机参数,治疗组明显低于对照组(P<0.05);治疗组气管插管率明显低于对照组,且上机时间(nCPAP、nIPPV、气管插管机械通气)也较对照组明显缩短(P<0.05),但两组患儿存活率及住院时间差异无统计学意义。结论:对于近足月呼吸窘迫综合征患儿,尽早明确诊断并在发病早期给予PS替代治疗,可提高此类患儿的生存率及预后,对降低早产儿病死率有重要意义!