Fatal COVID-19 in a neonate after probable late intrauterine transmission.

We report the case of a 35-week gestation infant girl born by emergent cesarean section for fetal distress in a woman with recent coronavirus disease 2019 (COVID-19). Tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using polymerase chain reaction (PCR) on the infant at 24 and 48 hours of life were negative. However, at 72 hours of life, the infant's respiratory status worsened, and a repeat SARS-CoV-2 PCR was positive. The infant developed leukopenia, thrombocytopenia, and progressive respiratory failure, and died on the ninth day of life. Pathologic examination of the placenta revealed findings consistent with COVID-19 placentitis, and SARS-CoV-2 RNA staining was positive, suggesting intrauterine transmission of the infection.

Jaundice and a testicular lump: a rare cause of malignant biliary obstruction.

Biliary obstruction from metastatic deposits in the pancreas is rare. We present a case of primary testicular lymphoma (PTL) with pancreatic metastasis. A 56-year-old man presented to the general surgical department with signs and symptoms of obstructive jaundice. A computed tomography scan revealed multiple pancreatic metastases and a right primary testicular malignancy. Histology and positron emission tomography scanning subsequently confirmed PTL with pancreatic metastases. Metastasis to the pancreas from primary testicular malignancy is extremely rare. There is variation in prognosis between primary and secondary pancreatic malignancies and therefore in atypical cases of malignant biliary obstruction consideration must be given to the rarer secondary malignancies.

Life expectancy inequalities in Wales before COVID-19: an exploration of current contributions by age and cause of death and changes between 2002 and 2018.

OBJECTIVES: The COVID-19 pandemic in Wales and the UK has highlighted significant and historic inequalities in health between social groups. To better understand the composition of these inequalities and inform planning after the pandemic, we undertook a decomposition of life expectancy inequalities between the most and least deprived quintiles for men and women by age and cause of death and explored trends between 2002 and 2018. STUDY DESIGN: Statistical decomposition of life expectancy inequalities by age and cause of death using routine population mortality datasets. METHODS: We used routine statistics from the Office for National Statistics for the period 2002-2018 on population and deaths in Wales stratified by age, gender, Welsh Index of Multiple Deprivation (WIMD) 2019 quintile and cause of death, categorised by International Classification of Disease, version 10, code into 15 categories of public health relevance. We aggregated data to 3-year rolling figures to account for low numbers of events in some groups annually. Next, we estimated life expectancy at birth by quintile, gender and period using life table methods. Lastly, we performed a decomposition analysis using the Arriaga method to identify the specific disease categories and ages at which excess deaths occur in more disadvantaged areas to highlight potential areas for action. RESULTS: Life expectancy inequalities between the most and least WIMD quintiles rose for both genders between 2002 and 2018: from 4.69 to 6.02 years for women (an increase of 1.33 years) and from 6.34 to 7.42 years for men (an increase of 1.08 years). Exploratory analysis of these trends suggested that the following were most influential for women: respiratory disease (1.50 years), cancers (1.36 years), circulatory disease (1.35 years) and digestive disease (0.51 years). For men, the gap was driven by circulatory disease (2.01 years), cancers (1.39 years), respiratory disease (1.25 years), digestive disease (0.79 years), drug- and alcohol-related conditions (0.54 years) and external causes (0.54 years). Contributions for women from respiratory disease, cancers, dementia and drug- and alcohol-related conditions appeared to be increasing, while among men, there were rising contributions from respiratory, digestive and circulatory disease. CONCLUSIONS: Life expectancy inequalities in Wales remain wide and have been increasing, particularly among women, with indications of worsening trends since 2010 following the introduction of fiscal austerity. As agencies recover from the pandemic, these findings should be considered alongside any resumption of services in Wales or future health and public policy.

Certification for vision impairment: researching perceptions, processes and practicalities in health and social care professionals and patients.

OBJECTIVES: To explore the patient experience, and the role of ophthalmologists and other health and social care professionals in the certification and registration processes and examine the main barriers to the timely certification of patients. DESIGN: Qualitative study. SETTING: Telephone interviews with health and social care professionals and patients in three areas in England. PARTICIPANTS: 43 health and social care professionals who are part of the certification or registration process. 46 patients certified as severely sight impaired (blind) or sight impaired (partially sighted) within the previous 12 months. RESULTS: Certification and registration are life changing for patients and the help they receive can substantially improve their lives. Despite this, ophthalmologists often found it difficult to ascertain when it is appropriate to certify patients, particularly for people with long-term conditions. Ophthalmologists varied in their comprehension of the certification process and many regarded certification as the 'final stage' in treatment. Administrative procedures meant the process of certification and registration could vary from a few weeks to many months. The avoidable delays in completing certification can be helped by Eye Clinic Liaison Officers (ECLO). CONCLUSIONS: A better understanding of the certification and registration processes can help improve standards of support and service provision for people who are severely sighted impaired or sight impaired. Better education and support are required for ophthalmologists in recognising the importance of timely referral for rehabilitative support through certification and registration. ECLOs can improve the process of certification and registration. Finally, better education is needed for patients on the benefits of certification and registration.

A point prevalence survey of antibiotic use in four acute-care teaching hospitals utilizing the European Surveillance of Antimicrobial Consumption (ESAC) audit tool.

The objective of this research was to assess current patterns of hospital antibiotic prescribing in Northern Ireland and to determine targets for improving the quality of antibiotic prescribing. A point prevalence survey was conducted in four acute teaching hospitals. The most commonly used antibiotics were combinations of penicillins including ß-lactamase inhibitors (33·6%), metronidazole (9·1%), and macrolides (8·1%). The indication for treatment was recorded in 84·3% of the prescribing episodes. A small fraction (3·9%) of the surgical prophylactic antibiotic prescriptions was for >24 h. The results showed that overall 52·4% of the prescribed antibiotics were in compliance with the hospital antibiotic guidelines. The findings identified the following indicators as targets for quality improvement: indication recorded in patient notes, the duration of surgical prophylaxis and compliance with hospital antibiotic guidelines. The results strongly suggest that antibiotic use could be improved by taking steps to address the identified targets for quality improvement.

Bronchoscopy in suspected pulmonary TB with negative induced-sputum smear and MTD(®) Gen-probe testing.

INTRODUCTION: In our institution, patients with suspected pulmonary TB undergo multiple induced-sputum sampling for microscopy, culture and nucleic acid amplification (NAA) with the MTD(®) Gen-probe assay. Those with negative induced-sputum results still suspected with TB are then referred for bronchoscopy. We sought to determine the diagnostic yield of bronchoscopy in these patients with negative initial induced-sputum results both via smear and NAA testing. METHODS: We identified 30 consecutive cases of suspected pulmonary TB between 2001 and 2007, who had undergone a diagnostic bronchoscopy after negative results on induced-sputum smears and the MTD(®) Gen-probe on at least 2 samples. RESULTS: The cohort (M = 20 & F = 10) had a median age of 37 (range 16-85 yrs); were predominantly foreign born (27/30); HIV-negative (29/30) individuals with strongly positive TST's (mean 18 + 5 mm). Induced-sputum cultures were negative for M-TB in all patients after a full 60-day incubation period. BAL was culture positive for M-TB in 3/30 cases (10%) with 2 strains being pan-sensitive and the third being INH resistant. BAL microscopy with acid-fast smear (n = 30) and BAL Gen-probe (n = 23) were negative in all cases. A third of the patients (9/27, 33%) with negative bronchoscopy results were treated for culture negative TB. Treatment for latent TB was initiated in 5/27 (18%) individuals whereas 13/27 (48%) received no further treatment. CONCLUSION: Bronchoscopy provided diagnostic confirmation of pulmonary TB in 10% of subjects at least 2 negative induced-sputum samples by smear microscopy and NAA testing.

Duct Excision is Still Necessary to Rule out Breast Cancer in Patients Presenting with Spontaneous Bloodstained Nipple Discharge.

Introduction. Spontaneous nipple discharge is the third most common reason for presentation to a symptomatic breast clinic. Benign and malignant causes of spontaneous nipple discharge continue to be difficult to distinguish. We analyse our experience of duct excisions for spontaneous nipple discharge to try to identify features that raise suspicion of breast cancer and to identify features indicative of benign disease that would be suitable for nonoperative management. Methods. Details of one hundred and ninety-four patients who underwent duct excision for spontaneous nipple discharge between 1995 and 2005 were analysed. Results. Malignant disease was identified in 11 (5.7%) patients, 4 invasive and 7 insitu, which was 10.2% of those presenting with bloodstained discharge. All patients with malignant disease had bloodstained discharge. Discharge due to malignant disease was more likely to be bloodstained than that due to benign causes (Fisher's exact test, 2-tailed P value = 0.00134). Conclusion. Our findings do not support a policy of conservative management of spontaneous bloodstained nipple discharge. Cases of demonstrable spontaneous bloodstained nipple discharge should undergo duct excision to prevent malignant lesions being missed.

What are the drivers of the UK media coverage of meticillin-resistant Staphylococcus aureus, the inter-relationships and relative influences?

Meticillin-resistant Staphylococcus aureus (MRSA) infection in the UK receives intense media attention. The nature of coverage, political responses and solutions offered has been questioned and the relationship between health professionals, the media and government policy needs greater understanding. We identified 2880 articles on MRSA published in 12 UK newspapers between 1994 and 2005, compared with 21 articles in six major US newspapers. To investigate the relative influences and relationships further, 68 weeks of coverage from 1990 to 2004 were analysed. The dates were selected based on publication dates of the ten most frequently cited articles on MRSA according the ISI Web of Science portal of Department of Health press releases on MRSA since 1997. Within this period, 351 news articles were published with members of the public and politicians representing 60% of sources quoted. Scientific articles, even those with the highest number of citations, have negligible influence on newspaper coverage. Simple solutions quoted in the newspaper articles focused almost exclusively on cleaning. The UK press exhibits a high interest in MRSA compared with that of the USA. Healthcare workers, experts and professional bodies have criticised the nature of media reporting, but have had little influence or involvement in the press. This may facilitate journalists, celebrities, the public and politicians to drive these stories unchecked and allow politics to address only the simplistic solutions generated.

Home monitoring of blood pressure in pregnancy at high risk of pre-eclampsia.

The early detection of pre-eclampsia is a major challenge in obstetric care. We report a case where pre-eclampsia was detected by home blood pressure monitoring between routine antenatal visits. This novel management approach allows early diagnosis and optimises antenatal care in fulminating disease.

A technology to measure multiple driving behaviors without self-report or participant reactivity.

An in-vehicle information system (IVIS) was used to videotape drivers (N = 61) without their knowledge while driving 22 miles in normal traffic. The drivers were told that they were participating in a study of direction following and map reading. Two data-coding procedures were used to analyze videotapes. Safety-related behaviors were counted during consecutive 15-s intervals of a driving trial, and the occurrence of certain safety-related behaviors was assessed under critical conditions. These two methods of data coding were assessed for practicality, reliability, and sensitivity. Interobserver agreement for the five different driving behaviors ranged from 85% to 95%. Within-subject variability in safe driving was more pronounced among younger drivers and decreased as a function of age. Contrary to previous research that has relied on self-reports, driver risk taking did not vary significantly as a function of gender. These results are used to illustrate the capabilities of the technology introduced here to design and evaluate behavior-analytic interventions to increase safe driving.

Rates of hospitalization for respiratory syncytial virus infection among children in medicaid.

OBJECTIVE: To determine rates of hospitalization associated with respiratory syncytial virus (RSV) infection among children with and without specific medical conditions. STUDY DESIGN: Retrospective cohort study of all children <3 years old enrolled in the Tennessee Medicaid program from July 1989 through June 1993 (248,652 child-years). RESULTS: During the first year of life, the estimated number of RSV hospitalizations per 1000 children was 388 for those with bronchopulmonary dysplasia, 92 for those with congenital heart disease, 70 for children born at < or = 28 weeks' gestation, 66 for those born at 29 to <33 weeks, 57 for those born at 33 to <36 weeks, and 30 for children born at term with no underlying medical condition. In the second year of life, children with bronchopulmonary dysplasia had an estimated 73 RSV hospitalizations per 1000 children, whereas those with congenital heart disease had 18 and those with prematurity 16 per 1000. Overall, 53% of RSV hospitalizations occurred in healthy children born at term. CONCLUSIONS: Children with bronchopulmonary dysplasia have high rates of RSV hospitalization until 24 months of age. In contrast, after the first year of life, children with congenital heart disease or prematurity have rates no higher than that of children at low risk who are <12 months old.

Reliable urine analysis in the management of hypertensive pregnancies.

OBJECTIVE: To determine the intra- and inter-observer precision of the Clinitek 50 automated urinalysis system. SETTING: A teaching hospital. METHODS: Urine samples were tested by seven operators with Multistix 8SG reagent strips, in duplicate and in replicates of five by the same operators, and by groups of four operators on the same samples. Precision was assessed using true urine samples and Chek-Stix control strips. RESULTS: All 32 samples tested in duplicate and in replicates of five agreed to within one colour block by between 99.4 and 100% for all eight analytes. Seven samples tested by four different operators also gave 100% agreement to within one colour block for nearly all analytes. All operators found the Clinitek 50 system to be quick and easy to use. CONCLUSION: The Clinitek 50 automated urinalysis device demonstrates high intra- and inter-observer precision for duplicate, multiple replicate and multiuser testing with consistent performance. There is potential to improve antenatal care by introducing this technology into hospital or home-based care.

Evaluation of a live, cold-passaged, temperature-sensitive, respiratory syncytial virus vaccine candidate in infancy.

A live-attenuated, intranasal respiratory syncytial virus (RSV) candidate vaccine, cpts-248/404, was tested in phase 1 trials in 114 children, including 37 1-2-month-old infants-a target age for RSV vaccines. The cpts-248/404 vaccine was infectious at 104 and 105 plaque-forming units in RSV-naive children and was broadly immunogenic in children >6 months old. Serum and nasal antibody responses in 1-2 month olds were restricted to IgA, had a dominant response to RSV G protein, and had no increase in neutralizing activity. Nevertheless, there was restricted virus shedding on challenge with a second vaccine dose and preliminary evidence for protection from symptomatic disease on natural reexposure. The cpts-248/404 vaccine candidate did not cause fever or lower respiratory tract illness. In the youngest infants, however, cpts-248/404 was unacceptable because of upper respiratory tract congestion associated with peak virus recovery. A live attenuated RSV vaccine for the youngest infant will use cpts-248/404 modified by additional attenuating mutations.

Safety and immunogenicity of adjuvanted and unadjuvanted subunit influenza vaccines administered intranasally to healthy adults.

Antigen-specific mucosal immunity is thought to be important for protection against influenza virus infection. Currently licensed parenteral influenza vaccines stimulate the production of serum antibodies, but are poor inducers of mucosal immunity. The adjuvant MF59 has been shown to enhance the humoral immune response to parenteral influenza vaccine in humans and the mucosal immune response to intranasally-administered influenza vaccine in mice. We conducted an open-label safety study followed by an observer-blind, randomized trial comparing the immune response to intranasally-administered subunit influenza vaccine adjuvanted with MF59, unadjuvanted subunit influenza vaccine, and placebo. Adverse reactions did not occur significantly more frequently in vaccinees than placebo recipients. Of 31 subjects receiving 2 doses of MF59-adjuvanted influenza vaccine, 19 (61%), 8 (26%), and 11 (35%) developed a mucosal IgA response to influenza A/H1N1, A/H3N2, and B, respectively. The percentage of subjects with a serum antibody response was slightly lower. The immune responses to adjuvanted vaccine were not significantly different from those to unadjuvanted vaccine. Both vaccines gave more frequent responses than seen in placebo recipients, indicating the potential of intranasal inactivated vaccines to stimulate local IgA responses.

Promises and challenges of live-attenuated intranasal influenza vaccines across the age spectrum: a review.

Despite the availability of inactivated influenza vaccines, influenza continues to cause considerable mortality in the elderly, and morbidity in all age groups. Cold-adapted, live-attenuated, intranasally administered influenza vaccines, first developed in the 1960s, have been tested in more than 10,000 volunteers and have been shown to be safe, well-tolerated, and immunogenic. Recent trials suggest that efficacy in children may be superior to that of inactivated vaccines, and efficacy in healthy adults may be similar to that of inactivated vaccines, although there are limited data comparing the two vaccines directly. Advantages of the live-attenuated vaccines include acceptability, ease of administration, and the potential for mass immunization. The possibility of substantially higher vaccination rates across all age groups brings promise for the development of herd immunity and greatly improved control of influenza in the future.

MCE activities and malathion resistances in field populations of the australian sheep blowfly (Lucilia cuprina).

Malathion resistance has been shown to be the result of a single point mutation in the LcalphaE7 gene in four independently isolated chromosomes of Lucilia cuprina. The resultant amino acid substitution specifies high malathion carboxylesterase (MCE) activity. We have assayed MCE activities and resistance to malathion in three sets of field-derived samples, two sets of isogenic lines and five mass populations, and show that resistance to malathion in these samples is associated with high MCE activity in both sets of isogenic lines and four of the five mass populations. Additional mechanisms contributing to MCE activity or malathion resistance may be present in one of the mass populations. A second point mutation in LcalphaE7 is responsible for conferring diazinon resistance by encoding an increased organophosphate (OP) hydrolase activity. We also assayed diazinon resistances from the same three samples and show that diazinon and malathion resistances were in complete disequilibrium, with two exceptions. One exception involves the mass population with additional resistance mechanism(s) and the other involves three isogenic lines that are resistant to both insecticides. The molecular data for these lines suggest that they carry a duplication of the LcalphaE7 gene.

Mucosal immune response to trivalent live attenuated intranasal influenza vaccine in children.

Intranasal trivalent, cold-adapted, live attenuated influenza vaccine (CAIV-T) is a promising alternative to inactivated vaccine for protection against influenza in children. However, correlates of immunity are not well defined. To determine the mucosal immune response to CAIV-T, 19 children ages 15-55 months were randomized to receive two doses of CAIV-T or placebo. Influenza-specific IgA to the haemagglutinin of each of three contemporary strains was measured in nasal washes collected pre- and postvaccination using a kinetic enzyme-linked immunosorbent assay. After two doses of study drug, 62, 69 and 85% of CAIV-T recipients demonstrated a mucosal IgA response to influenza A/H1N1, A/H3N2, and B strains respectively; in comparison, 33, 0 and 17% of placebo recipients demonstrated an IgA response to the same strains (p = 0.35, 0.01 and 0.01). Overall, seropositive vaccinees were 4.5 times more likely to develop a mucosal immune response than an HAI response (p = 0.015). Two doses of CAIV-T induce a mucosal IgA response to all three influenza vaccine antigens in the majority of children. In addition, a mucosal antibody response may be the only indication of a vaccine take in a seropositive child.

Allograft bone. The influence of processing on safety and performance.

Advances in tissue processing technology have been important for the successful use of bone allografts. The challenge is to prepare allografts that are well cleaned, sterile, and free of viruses while still preserving the natural biologic and biomechanical properties of the tissue. This article discusses how processing techniques aimed at achieving safety and sterility can affect the properties vital for graft incorporation and healing.