Double Jeopardy: A Distinct Mortality Pattern Among Preterm Infants with Congenital Heart Disease.

Contemporary United States (US) data on the survival of preterm infants with congenital heart disease (CHD) are unavailable despite the over-representation of CHD and improving surgical outcomes in the preterm population. The aim of this study is to use population-based data to compare 1-year survival and early mortality (< 3 days) by gestational age (GA) between preterm infants with and without cyanotic CHD (CCHD) in the US. This national retrospective cohort included all liveborn, preterm infants between 21 and 36 weeks GA with a birth certificate indicating the presence or absence of CCHD (n = 2,654,253) born between 2014 and 2019 in the US. Data were provided by the US Center for Disease Control database linking birth and death certificates. Of liveborn preterm infants, 0.13% (n = 3619) had CCHD. 1-year survival was significantly lower in infants 23-36 weeks with CCHD compared to those without. The greatest survival gap occurred between 28 and 31 weeks (28 weeks adjusted risk difference 37.5%; 95% CI 28.4, 46.5; 31 weeks 37.9%; 30.5, 45.3). Early mortality accounted for more than half of deaths among infants 23-31 weeks with CCHD (23 weeks-68%, CI 46.7, 83.7; 31 weeks-63.9%, 52.9, 73.6). Survival trends demonstrated worsened 1-year survival in infants 35-36 weeks with CCHD over the study period. The pattern of mortality for preterm infants with CCHD is distinct from those without. The significant survival gap in the very preterm population and notably high rate of early death in the infants with CCHD calls for renewed attention to early neonatal intensive care for this dually affected population.

Resuscitation, survival and morbidity of extremely preterm infants in California 2011-2019.

OBJECTIVE: To describe changes over time in resuscitation, survival, and morbidity of extremely preterm infants in California. STUDY DESIGN: This population-based, retrospective cohort study includes infants born ≤28 weeks. Linked birth certificates and hospital discharge records were used to evaluate active resuscitation, survival, and morbidity across two epochs (2011-2014, 2015-2019). RESULTS: Of liveborn infants, 0.6% were born ≤28 weeks. Active resuscitation increased from 16.9% of 22-week infants to 98.1% of 25-week infants and increased over time in 22-, 23-, and 25-week infants (p-value ≤ 0.01). Among resuscitated infants, survival to discharge increased from 33.2% at 22 weeks to 96.1% at 28 weeks. Survival without major morbidity improved over time for 28-week infants (p-value < 0.01). CONCLUSION: Among infants ≤28 weeks, resuscitation and survival increased with gestational age and morbidity decreased. Over time, active resuscitation of periviable infants and morbidity-free survival of 28-week infants increased. These trends may inform counseling around extremely preterm birth.

A cost-utility analysis of SIR-Spheres Y-90 resin microspheres versus best supportive care in the treatment of unresectable metastatic colorectal cancer refractory to chemotherapy in the UK.

BACKGROUND: Limited treatment options are available in chemotherapy-refractory or -intolerant metastatic colorectal cancer (mCRC). The objective of the present analysis was to evaluate the cost-utility of SIR-Spheres Y-90 resin microspheres relative to best supportive care (BSC) in the treatment of chemotherapy refractory mCRC from the perspective of the UK national healthcare payer. METHODS: A cost-utility model was developed in Microsoft Excel to simulate transitions from progression-free survival to post-progression survival and death in patients with mCRC. Unit costs were captured in 2019 pounds sterling (GBP) based on the literature, formulary listings, and National Health Service (NHS) England reference costs. Future costs and effects were discounted at 3.5% per annum. A series of one-way sensitivity analyses, and probabilistic sensitivity analysis (PSA) were conducted. RESULTS: The base case analysis showed that SIR-Spheres Y-90 resin microspheres would result in an increase in discounted quality-adjusted life years gained from 0.69 quality-adjusted life years (QALYs) to 1.50 QALYs, with an associated increase in cost from GBP 15,268 to GBP 34,168 yielding an incremental cost-utility ratio of GBP 23,435 per QALY. PSA showed that there would be a 56% likelihood that SIR-Spheres Y-90 resin microspheres would be cost-effective relative to BSC at a willingness-to-pay threshold of GBP 30,000 per QALY gained. CONCLUSIONS: This cost-utility analysis showed that, relative to BSC, SIR-Spheres Y-90 resin microspheres would be a cost-effective treatment option for patients with mCRC in the UK setting from the national healthcare payer perspective.

Pregnancy outcomes in facility deliveries in Kenya and Uganda: A large cross-sectional analysis of maternity registers illuminating opportunities for mortality prevention.

INTRODUCTION: As facility-based deliveries increase globally, maternity registers offer a promising way of documenting pregnancy outcomes and understanding opportunities for perinatal mortality prevention. This study aims to contribute to global quality improvement efforts by characterizing facility-based pregnancy outcomes in Kenya and Uganda including maternal, neonatal, and fetal outcomes at the time of delivery and neonatal discharge outcomes using strengthened maternity registers. METHODS: Cross sectional data were collected from strengthened maternity registers at 23 facilities over 18 months. Data strengthening efforts included provision of supplies, training on standard indicator definitions, and monthly feedback on completeness. Pregnancy outcomes were classified as live births, early stillbirths, late stillbirths, or spontaneous abortions according to birth weight or gestational age. Discharge outcomes were assessed for all live births. Outcomes were assessed by country and by infant, maternal, and facility characteristics. Maternal mortality was also examined. RESULTS: Among 50,981 deliveries, 91.3% were live born and, of those, 1.6% died before discharge. An additional 0.5% of deliveries were early stillbirths, 3.6% late stillbirths, and 4.7% spontaneous abortions. There were 64 documented maternal deaths (0.1%). Preterm and low birthweight infants represented a disproportionate number of stillbirths and pre-discharge deaths, yet very few were born at ≤1500g or <28w. More pre-discharge deaths and stillbirths occurred after maternal referral and with cesarean section. Half of maternal deaths occurred in women who had undergone cesarean section. CONCLUSION: Maternity registers are a valuable data source for understanding pregnancy outcomes including those mothers and infants at highest risk of perinatal mortality. Strengthened register data in Kenya and Uganda highlight the need for renewed focus on improving care of preterm and low birthweight infants and expanding access to emergency obstetric care. Registers also permit enumeration of pregnancy loss <28 weeks. Documenting these earlier losses is an important step towards further mortality reduction for the most vulnerable infants.

Cohort study of neonatal resuscitation skill retention in frontline healthcare facilities in Bihar, India, after PRONTO simulation training.

BACKGROUND: Use of simulation in neonatal resuscitation (NR) training programmes has increased throughout low-income and middle-income countries. Many of such programmes have demonstrated a positive impact on NR knowledge and skill acquisition along with reduction of early neonatal mortality and fresh stillbirth rates. However, NR skill retention after simulation programmes remains a challenge. METHODS: This study assessed facility level NR skill retention after PRONTO International's simulation training in Bihar, India. Training was conducted within CARE India's statewide in-job, on-site Apatkaleen Matritva evam Navjat Tatparta mentoring programme as part of a larger quality improvement and health systems strengthening initiative. Public sector facilities were initially offered training, facilitated by trained nursing graduates, during 8-month phases between September 2015 and January 2017. Repeat training began in February 2018 and was facilitated by peers. NR skills in simulated resuscitations were assessed at the facility level at the midpoint and endpoint of initial training and prior to and at the midpoint of repeat training. RESULTS: Facilities administering effective positive pressure ventilation and assessing infant heart rate increased (31.1% and 13.1%, respectively, both p=0.03) from midinitial to postinitial training (n=64 primary health centres (PHCs) and 192 simulations). This was followed by a 26.2% and 20.9% decline in these skills respectively over the training gap (p≤0.01). A significant increase (16.1%, p=0.04) in heart rate assessment was observed by the midpoint of repeat training with peer facilitators (n=45 PHCs and 90 simulations). No significant change was observed in other skills assessed. CONCLUSIONS: Despite initial improvement in select NR skills, deterioration was observed at a facility-level post-training. Given the technical nature of NR skills and the departure these skills represent from traditional practices in Bihar, refresher trainings at shorter intervals are likely necessary. Very limited evidence suggests peer simulation facilitators may enable such increased training frequency, but further study is required.

Obesity, dieting, and multiple sclerosis.

BACKGROUND: Obesity is common in the United States and is associated with a higher risk of relapse and comorbidities, and increased disease progression, in people with MS. METHODS: We examined the prevalence of overweight and obesity in the MS Sunshine Study, a matched case-control study of multiple sclerosis in Southern California (470 cases, 519 controls). We reported the proportion of participants who adopted a specific diet for nutrition or weight loss purposes, and identified independent predictors of dieting. RESULTS: In the total population, 32% and 37% were overweight and obese, respectively. Case participants were no more likely to adopt a specific diet for nutrition or weight loss purposes than control participants (10% and 11%, respectively). Being obese, younger, female or non-Hispanic were independently associated with dieting. CONCLUSION: Despite the evidence that obesity can worsen MS prognosis, and the high prevalence of overweight/obesity, case participants were no more likely to adopt a specific diet than control participants. Improved nutrition education may help people with MS make healthy dietary changes for nutrition or weight loss purposes.

Selective arterial embolisation for intractable vaginal haemorrhage in genital tract malignancies.

PURPOSE OF INVESTIGATION: Embolisation of the internal iliac artery has been described as an effective and safe method of treating massive vaginal haemorrhage in small series of advanced uterine cancer and case reports of cervical cancer. Selective embolization of the bleeding vessel is potentially less morbid. The aim of this study was to assess the efficacy of selective arterial embolisation (SAE) in controlling intractable haemorrhage due to gynaecological malignancy. MATERIALS AND METHODS: This retrospective observational study comes from in a tertiary cancer center with 300 new gynecologic cancers per annum. The authors reviewed all gynecology cancer patients who had intractable major vaginal haemorrhage in the first five years following the introduction of selective arterial embolisation at their unit. The outcomes measured were the control of acute haemorrhage and discharge to planned pathway of treatment. RESULTS: SAE was successful in all cases. Identification of the bleeding point facilitated highly selective embolisation in more than half of the patients. The uterine arteries were embolised in the remaining cases. Bleeding stopped immediately. The expedient control of haemorrhage facilitated early discharge to commencement/continuation of radiation treatment or palliative care as appropriate. CONCLUSIONS: Since the introduction of SAE the authors have avoided emergency radiotherapy, surgery, and repeat vaginal packing in patients with intractable vaginal bleeding due to gynaecological cancer. Patients were discharged to their appropriate treatment pathways in a timely manner. The authors recommend the application of SAE.

The cost of illness of atrial fibrillation: a systematic review of the recent literature.

Atrial fibrillation (AF) is the most common cardiac arrhythmia, its prevalence increasing markedly with age. Atrial fibrillation is strongly associated with increased risk of morbidity, including stroke and thromboembolism. There is growing awareness of the economic burden of AF due to ageing populations and constrained public finances. A systematic review was performed (1990-2009). Cost studies for AF or atrial flutter were included; acute-onset and post-operative AF were excluded. Total, direct, and indirect costs were extracted. Of 875 records retrieved, 37 studies were included. The cost of managing individual AF patients is high. Direct-cost estimates ranged from $2000 to 14,200 per patient-year in the USA and from €450 to 3000 in Europe. This is comparable with other chronic conditions such as diabetes. The direct cost of AF represented 0.9-2.4% of the UK health-care budget in 2000 and had almost doubled over the previous 5 years. Inpatient care accounted for 50-70% of annual direct costs. In the USA, AF hospitalizations alone cost ∼$6.65 billion in 2005. In this first systematic review of the economic burden of AF, hospitalizations consistently represented the major cost driver. Costs and hospitalizations attributable to AF have increased markedly over recent decades and are expected to increase in future due to ageing populations.

Cost-effectiveness of venous thromboembolism prophylaxis in total hip and knee replacement surgery: the evolving application of health economic modelling over 20 years.

OBJECTIVES: In the last two decades, there has been considerable evolution of methods for cost-effectiveness modelling. Some of the first models were developed in the area of venous thromboembolism (VTE) prophylaxis. Hence, this area can serve as an important example to illustrate evolving standards. Our objectives are to document evolving methodology by describing VTE models, assess their critical strengths and weaknesses, and inform future advances for models in this therapeutic area. RESEARCH DESIGN AND METHODS: A systematic review of economic models of primary VTE prevention following hip and knee replacement surgery was undertaken. Electronic searches of PubMed, EMBASE, the Cochrane library, and grey literature were conducted (1985-2006). Reference lists of included articles and reviews were examined for relevant studies. RESULTS: Twenty-nine cost-effectiveness models were identified. Nineteen other cost-effectiveness analyses were excluded because they were not model-based; 16 were simple cost calculations and three were analyses of resource use data collected alongside clinical trials. The majority of models (24) were constructed as decision trees, frequently utilising previously published model structures, with some adaptation for new comparators, and/or addition of relevant events omitted by earlier models (e.g., bleeding due to prophylactic treatment). Later models have included Markov processes to model potential long-term consequences of VTE (recurrent VTE and post-thrombotic syndrome) over longer time horizons. Systematic identification of clinical evidence and more sophisticated analysis methods (e.g., Bayesian mixed-treatment comparisons and probabilistic sensitivity analyses) have recently been introduced. CONCLUSIONS: Model structures have evolved substantially in this highly studied therapeutic area, with improvements made to the model structure, the comprehensiveness of clinical evidence included, and the underlying calculation methodology.

Multidrug-resistant tuberculosis in bone marrow transplant recipient.

Multidrug-resistant tuberculosis (TB) is an increasing problem worldwide, however only three cases have been previously described in transplant recipients, especially involving lung and heart transplant. We describe a case of multidrug-resistant TB in an allogenic bone marrow transplant recipient with good response to second-line therapy.

Prospective audit of adverse reactions occurring in 459 primary antibody-deficient patients receiving intravenous immunoglobulin.

Intravenous immunoglobulin (IVIG) is used as the standard replacement therapy for patients with primary antibody deficiencies. A previous study of adverse reactions in patients self-infusing at home over 1 year showed an overall reaction rate of 0.7%. A larger prospective study is reported here, involving a greater number of immunology centres and including children and adults who received infusions from medical or nursing staff as well as those self-infusing. Four hundred and fifty-nine patients were entered into this study and 13 508 infusions were given. The study showed that no severe reactions occurred and the reaction rate was low at 0.8%. This figure could have been lower, 0.5%, if predisposing factors responsible for some reactions had been considered before infusion. In conclusion, the study shows the importance of ongoing training for patients and staff to recognize the predisposing factors to prevent avoidable reactions. Because none of these reactions were graded as severe, the present guidance to prescribe self-injectable adrenaline for patients infusing outside hospital should be reviewed.

The use of self infused intravenous immunoglobulin home therapy in the treatment of acquired chronic demyelinating neuropathies.

High dose intravenous immunoglobulin therapy is becoming the established maintenance treatment for several neurological conditions. Therapeutic immunoglobulin is expensive and its administration is time consuming. Efficacy is variable and must be closely monitored. Here, we show that self infused immunoglobulin at home, combined with daily functional strength diaries to predict dose and dosage intervals, is effective, time saving, and convenient for both patients and medical staff.

Surveillance of adverse reactions in patients self-infusing intravenous immunoglobulin at home.

This is the first prospective study of adverse reactions occurring in primary-antibody-deficient patients self-infusing intravenous immunoglobulin at home. One hundred nineteen patients, already self-infusing at home, were entered into the study. They had been fully instructed about all aspects of adverse reactions, including their prevention and treatment. In the event of any adverse reaction, a form was completed detailing the product, the dose, the symptoms that occurred and the time they lasted, the rate of infusion, and other relative information such as predisposing factors and any medication taken. The severity of reactions were classified as mild, moderate, or severe. The total number of reactions documented was 19 in 2031 infusions, and all resolved without medical aid. No serious reactions occurred. Excluding those reactions in which predisposing factors were identified, the overall reaction rate was 0.7%. In conclusion the study showed the reaction rate in patients self-infusing intravenous immunoglobulin at home was low following formal training of selected patients at recognized training centers.

Immunoglobulin replacement in patients with chronic lymphocytic leukaemia: a comparison of two dose regimes.

Previous studies have shown that intravenous immunoglobulin (IVIg) therapy is useful prophylaxis against infection in patients with secondary hypogammaglobulinaemia due to a low-grade lymphoproliferative disease. This randomized double-blind study was undertaken to determine prospectively the dose regime required. 34 such patients received IVIg at either 500 or 250 mg/kg every 4 weeks for 1 year. There was no significant difference in the rates of serious infections between the two groups of patients, which were well matched for disease and laboratory parameters. The rates of infection seen were similar to those in IVIg groups of previous studies and strikingly different from those in the placebo group in the previously randomized placebo-controlled study.

Expression of human thyroid peroxidase in insect cells using recombinant baculovirus.

The baculovirus expression system was used to overexpress recombinant human thyroid peroxidase. Sf-9 cells infected with the recombinant virus AcMNPV-hTPO synthesized hTPO protein (hTPO-bac) immunogenic on Western blots when probed with either rabbit anti-TPO peptide sera or pooled human anti-TPO sera (MS12/89). hTPO-bac was a major constituent of the membrane fraction from the infected cells, constituting 14.9% and 10.1% of the 1% deoxycholate-soluble and insoluble fractions, respectively, as judged by densitometry. Recombinant hTPO-bac was extracted from cellular membranes with 1% deoxycholate and partially purified by Sepharose 6B column chromatography. Specific immunoreactivity of MS12/89 to hTPO-bac on microtiter plates was seen using ELISA. Detergent extract from wild-type virus-infected Sf-9 cells was used as background control antigen; no specific reactivity to either hTPO-bac or control antigen was seen with control sera. To determine antigenic potency, MS12/89 was incubated with increasing concentrations of various preparations of hTPO antigen and with ovalbumin as control. The capacity of the partially purified hTPO-bac to immunoneutralize human anti-hTPO standard at 50% inhibition of binding was 0.01 U/microgram hTPO-bac (NIBSC Units), compared with 0.5 U/microgram and 0.06 U/microgram for natural hTPO and CHO-hTPO, respectively. When ELISA was performed using clinical samples of human sera to detect hTPO autoantibodies, results using hTPO-bac correlated well with those using hTPO from Graves' thyroid tissue (r = 0.85, p = 0.02) and those using recombinant hTPO from Chinese hamster ovary cells (hTPO-CHO) (r = 0.85, p = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of serum thyrotropin levels on the concentration of messenger RNA for thyroid peroxidase in the rat.

The effect of serum TSH on rat thyroid peroxidase mRNA levels was studied in order to investigate the regulation of thyroid peroxidase gene expression in vivo. A nearly full-length rat thyroid peroxidase cDNA clone was isolated from a bacteriophage cDNA library synthesized using poly A+ RNA isolated from the thyroids of propylthiouracil-treated rats. cDNA probes derived from this clone were used to study rat thyroid peroxidase mRNA levels in response to the level of serum TSH. Two major rat thyroid peroxidase mRNA bands were detected on Northern blots of total cellular RNA (at 3.2 kb and at 3.7 kb). Injection of thyroxine, which lowered the levels of serum TSH, also lowered the steady-state levels of both rat thyroid peroxidase mRNAs, whereas treatment with methimazole, which increased serum TSH, increased both rat thyroid peroxidase mRNA levels. In hypophysectomized rats 10 days postoperative, very low levels of thyroid peroxidase mRNA were observed. Injection of bovine TSH (1 IU/day) increased rat thyroid peroxidase mRNA expression, preferentially in the 3.2 kb band. These results clearly demonstrate that TSH regulates rat thyroid peroxidase mRNA levels in vivo.

Use of intravenous immunoglobulin in chronic lymphocytic leukemia. A brief review.

Chronic lymphocytic leukemia (CLL) is a disorder with multiple defects leading to an increased susceptibility to infection. Hypogammaglobulinemia is present in about 20% to 70% of patients with CLL. Intravenous immunoglobulin (IVIG) supplementation (400 mg/kg body weight every 3 weeks) prevented bacterial infections in these patients. An ongoing study is being conducted to compare doses of 250 mg/kg/mo with those of 500 mg/kg/mo in 36 patients included so far. As of this writing, the rate of infection in the two treatment groups was not significantly different, and no substantial loss of protection against bacterial infection was found in the lower-dose group. It seems likely that the lower dose is almost as effective as the standard therapy. If this is so, cost savings would be substantial.