Secondary non-invasive prenatal screening for fetal trisomy: an effectiveness study in a public health setting.

OBJECTIVE: To evaluate the effectiveness of secondary screening using non-invasive prenatal testing (NIPT) in a routine NHS setting including test performance, turn-around times (TATs) and no-call (failure to obtain result) rates. To examine the influence of maternal and fetal characteristics on test performance. DESIGN: Retrospective cohort. SETTING: London teaching hospital. SAMPLE: A total of 8651 pregnancies undergoing screening for fetal trisomy using NIPT provided by an NHS cell-free DNA screening laboratory - the SAFE laboratory. METHODS: Screening test evaluation and TATs. Univariate and multivariate logistic regression analysis to identify significant predictors of no-call results and reported by low fetal fraction (<2%), very high fetal fraction (>40%) and processing failure. MAIN OUTCOME MEASURES: Test performance, TATs and no-call rates, factors affecting no-call results. RESULTS: Average TAT was 4.0 days (95% CI 4.0-4.2 days). Test sensitivities for trisomies 21 and 13/18 were 98.9% (95% CI 95.9-99.9%) and 90.4% (95% CI 80.0-96.8%), respectively. The overall no-call rate was 32/8651 (0.37%, 95% CI 0.26-0.52%). The overall risk of a no-call result was influenced by gestational age, dichorionic twin pregnancy, history of malignancy and pregnancies affected by trisomy 13/18, but not by maternal weight or use of low-molecular-weight heparin. CONCLUSIONS: High-throughput NIPT can be effectively embedded into a public health NHS setting. TATs of 4 days and no-calls of <0.5% were well within clinically desirable tolerances. Gestational age, maternal weight, assisted reproductive techniques, use of low-molecular-weight heparin and past history of malignancy did not have major impacts on test no-call rates and should not constitute reasons for withholding the option of NIPT from women. TWEETABLE ABSTRACT: Turn-around times of 4 days, no-call (test failure) rates of 0.37% and highly accurate NIPT can be successfully embedded in the NHS.

Penicillin-resistant Streptococcus pneumoniae in metropolitan New York hospitals: case control study and molecular typing of resistant isolates.

During the 4-month period from January to April, 1998, 476 patients with Streptococcus pneumoniae infections were detected in 12 metropolitan New York hospitals and 112 penicillin-resistant (PRP) isolates (24%) were identified in 11 institutions. A case control study of 100 patients with penicillin-resistant and susceptible pneumococci from four of the widely dispersed hospitals revealed a high incidence of underlying medical illnesses in adult patients (74%), a preponderance of patients with pneumonia (63%), and a majority of patients who had underlying risk factors for pneumonia or invasive disease (51%). In this limited case control study, no difference was noted between cases and controls regarding known risk factors for penicillin-resistant pneumococcal infections. The percentage of single-patient PRP isolates varied among individual hospitals but the mean percentages of PRP from the four participating University Medical Centers and seven community hospitals were similar: 26% and 22% respectively. By E-test, 60% and 26% were high-level penicillin and ceftriaxone resistant, respectively. Pulsed-field gel electrophoresis identified 26 chromosomal macrorestriction patterns among the 103 PRP isolates available for analysis, but almost half (50 isolates or 48%) of these belong to two drug-resistant internationally spread clones, SP(23)-1 and SP(9/14)-3, that were detected in all hospitals and were recovered from invasive and noninvasive sites in both children and adults.

The effect of an ipriflavone-containing supplement on urinary N-linked telopeptide levels in postmenopausal women.

Osteoporosis is a significant health concern to our aging population. We report here the results of a pilot placebo-controlled trial of a dietary supplement containing ipriflavone, calcium, and vitamin D on a urinary marker of bone breakdown in postmenopausal women. Seven postmenopausal women not currently receiving hormone replacement therapy received either an ipriflavone-containing supplement or placebo for 3 months. Urinary N-linked telopeptides, a marker of bone breakdown, declined by 29% in those receiving the supplement, whereas an increase in this marker was observed in the group receiving the placebo. No changes were observed in salivary hormone measurements. Although our sample size was small, to the best of our knowledge, this is the first report that demonstrates changes in N-linked telopeptide levels as a result of consuming an ipriflavone-containing product. Our findings confirm those of other researchers that demonstrate the usefulness of ipriflavone at slowing the progression of bone loss and suggest that measuring N-linked telopeptides may be a useful tool to assess therapeutic efficacy.

Distribution of methicillin-resistant Staphylococcus aureus clones among health care facilities in Connecticut, New Jersey, and Pennsylvania. .

A previous surveillance study conducted in 12 hospitals in New York City in 1996 identified a unique multidrug-resistant genetic lineage of methicillin-resistant Staphylococcus aureus (MRSA) that was widespread and accounted for as much as 42% of all the MRSA isolates. The purpose of the study described here was to determine possible geographic spread of this New York clone of MRSA to neighboring states. Single-patient MRSA isolates (258) from 29 health care facilities in Connecticut (CT), New Jersey (NJ), and Pennsylvania (PA) were collected during the calendar year 1998. DNA typing, consisting of fingerprinting of chromosomal macrorestriction patterns generated by SmaI digestion followed by pulsed-field gel electrophoresis (PFGE), identified 22 patterns. PFGE type A, closely related to the PFGE type of the previously identified New York clone, accounted for 154 (60%) of 258 isolates. The clone was detected in all facilities, was predominant in 19 of the 29 health care centers, and accounted for 92% of the MRSA isolates collected in PA. The overwhelming majority of MRSA with PFGE type A was also resistant to erythromycin, ciprofloxacin, and clindamycin. One of the two most common PFGE subtypes detected in the three states sampled (PFGE subtype A1) had an identical PFGE pattern to that of the previously described vancomycin-resistant strain of S. aureus (VISA) recently detected in a hospital in Westchester, NY. The second most frequent MRSA clone with PFGE type E and accounting for 26% (68/258 isolates), also described earlier in the 12 New York City hospitals, was resistant not only to erythromycin, ciprofloxacin, and clindamycin, but also to gentamicin and sulfamethoxazole-trimethoprim as well. The unique multidrug resistance pattern of this second clone and its geographic distribution accounted for the differences observed in the frequency of multidrug resistance among MRSA isolates recovered in the three states. The pandemic Iberian clone recently detected in New York City was not detected among the 258 MRSA isolates recovered in CT, NJ, and PA.

Heterogeneously vancomycin-resistant Staphylococcus epidermidis strain causing recurrent peritonitis in a dialysis patient during vancomycin therapy.

Methicillin-resistant Staphylococcus epidermidis (MRSE) was recovered over a 2-month period from the dialysis fluid of a peritoneal dialysis (PD) patient who experienced recurrent episodes of peritonitis during therapeutic and prophylactic use of vancomycin. Characterization of five consecutive MRSE isolates by molecular and microbiological methods showed that they were representatives of a single strain, had reduced susceptibility to vancomycin, did not react with DNA probes specific for the enterococcal vanA or vanB gene, and showed characteristics reminiscent of the properties of a recently described vancomycin-resistant laboratory mutant of Staphylococcus aureus. Cultures of these MRSE isolates were heterogeneous: they contained-with a frequency of 10(-4) to 10(-5)-bacteria for which vancomycin MICs were high (25 to 50 microg/ml) which could easily be selected to "take over" the cultures by using vancomycin selection in the laboratory. In contrast, the five consecutive MRSE isolates recovered from the PD patient during virtually continuous vancomycin therapy showed no indication for a similar enrichment of more resistant subpopulations, suggesting the existence of an "occult" infection site in the patient (presumably at the catheter exit site) which was not accessible to the antibiotic.

Leprosy control in the Northern Territory.

An epidemic of leprosy occurred among Aboriginal people of the Top End of the Northern Territory following its introduction towards the end of the 19th Century. The extent of this outbreak became apparent through community surveys conducted in the 1950s which revealed that one in 10 Aboriginal people in some areas were affected by leprosy. Initial control activities were outbreak-focused, directed at case finding and management. Case finding was by systematic community survey. Case management included appropriate rehabilitation and reconstructive surgery. Regular review of treated patients ensured early detection of relapse and detection and treatment of sequelae. Education and full participation of Aboriginal health workers in the diagnosis and management of cases provided local expertise at the hospital and community level. The case detection rate fell from 270 per 100,000 in the Aboriginal population in 1951 to four per 100,000 in 1997. Elimination of transmission is now the objective of the control program. Combining of the tuberculosis and leprosy control activities of the Territory Health Service in 1996 resulted in increased efficiency of the mycobacterial services.

Outbreak in a New York City teaching hospital burn center caused by the Iberian epidemic clone of MRSA.

During an 18-month period in a burn center (January 1995 through June 1996), 109 single-patient MRSA isolates were identified and 102 isolates (94%) were available for DNA fingerprinting. Ninety-nine isolates (97%) carried the mecA polymorph I and Tn554 type E. Pulsed-field electrophoresis (PFGE) identified 8 patterns, of which 60 isolates were of pattern F2. The I:E:F clonal type and a stable drug multidrug resistant phenotype (sensitivity only to trimethoprim/sulfamethoxazole and vancomycin) indicated that these isolates were closely related to the Iberian clone of MRSA, which is widely spread in Europe. The initial source of I:E:F isolates was sputum 49%, blood 23%, wound 16%, urine 7%, and intravascular catheter tip 5%. Fifty-four percent of patients had smoke inhalation injury, and 51/53 required intubation or tracheostomy. Forty-three isolates were considered invasive (positive blood culture). The overall mortality was 30%. Despite infection control measures, the I:E:F clone continued to be recovered from patients during the 18 months of study. This outbreak is the first known report of the Iberian MRSA clone in the United States.

Leprosy in the tropics and Australia.

Leprosy is no longer the feared disease of the past, but it still causes significant morbidity in countries where it is endemic, and it is estimated that up to 2500 million people are at risk of contracting the disease. Control with dapsone monotherapy over the past 20-30 years has been effective in some countries but secondary and, more recently, primary drug resistance is now widespread. This situation prompted the development of multidrug therapy regimens which are proving highly effective. Here the natural history and clinical features are described, as well as the history and impact of leprosy in Australia. Early diagnosis and the current multidrug regimens offer hope for long-term control of the disease.

The fate of the left kidney after end renosplenic shunt in experimentally induced extrahepatic portal hypertension.

Extrahepatic portal hypertension was induced in the rabbit by a one-stage complete ligation of the portal vein. End renal vein to side splenic vein shunts (renosplenic) were performed with haemorrhagic necrosis of the left kidney occurring after ligation of the left renal vein lateral to the adrenolumbar tributary. Thus the ureteric, lumbar, and pericapsular collaterals cannot adequately drain the left kidney. Ligation of the left renal vein on the medial side of the adrenolumbar tributary maintained a patent left renal vein in all cases with 60% of left kidney biopsies showing no histological evidence of changes to glomeruli or tubules, and the remainder showing early acute tubular necrosis.

Freeze-dried microarterial allografts.

Rehydrated freeze-dried microarterial allografts were implanted to bridge arterial defects using New Zealand White rabbits as the experimental model. Segments of artery from the rabbit ear and thigh were harvested and preserved for a minimum of 2 weeks after freeze-drying. These allografts, approximately 1 mm in diameter and ranging from 1.5 to 2.5 cm in length, were rehydrated and then implanted in low-pressure and high-pressure arterial systems. Poor patency was noted in low-pressure systems in both allografts and autografts, tested in 12 rabbits. In the high-pressure arterial systems, allografts that were freeze-dried and reconstituted failed in a group of 10 rabbits with an 8-week patency rate of 30 percent. Gamma irradiation in an effort to reduce infection and antigenicity of grafts after freeze-drying was associated with a patency rate of 10 percent at 8 weeks in this system in another group of 10 rabbits. Postoperative cyclosporin A therapy was associated with a patency rate of 22.2 percent in the high-pressure arterial system in a 9-rabbit group. Control autografts in this system in a group of 10 rabbits showed a 100 percent patency at 8 weeks. Microarterial grafts depend on perfusion pressure of the vascular bed for long-term patency. Rehydrated freeze-dried microarterial allografts do not seem to function well in lengths of 1 to 2.5 cm when implanted in a high-pressure arterial system. Freeze-dried arterial allografts are probably not antigenic.

Clinical significance of changes in serum proteins, immunoglobulins, and autoantibodies in leprosy.

Changes in the level of acute phase reactants such as C-reactive protein (CRP), serum globulins, and autoantibodies have been reported previously in patients with leprosy, particularly at the lepromatous end of the spectrum. The clinical significance of these findings was investigated by comparing the same parameters of humoral immune function in populations of Australian Aboriginals with stable treated leprosy and relevant contact groups including a) noninfected European sporadic contacts and b) healthy Aboriginal relatives of patients with confirmed leprosy. Raised levels of CRP and immunoglobulins and the higher frequency of autoantibodies seen in leprosy patients compared with sporadic contacts are probably related to differences in the incidence of nonleprous infection rather than to leprosy per se. Comparable results were obtained in the leprosy patients and their family contacts. The data highlight the need to use antigen-specific assays for determining the significance of changes in acute phase reactants and for distinguishing between the primary and secondary effects of Mycobacterium leprae infection.

Prosthodontics. Urgent care.

There are an infinite number of responses to prosthodontic urgent care situations. A knowledge of acrylic resins combined with imagination and a clear understanding of the patient's chief complaint will allow the dentist to respond in an effective manner.

Nerve calcification caused by leprosy in northern territory aboriginals.

Three cases of nerve calcification caused by leprosy (Hansen's disease) in Aboriginal patients from the Northern Territory of Australia are reported. This is a rare manifestation of the disease and is the result of direct involvement of peripheral nerves with abscess formation and is usually seen in tuberculoid or borderline types of leprosy.

Peripheral nerve biopsies in the diagnosis of leprosy in Aboriginal patients from the Northern Territory of Australia.

In the 12 years from 1964 to 1976, 171 peripheral nerve biopsies were taken from 81 Aboriginal patients in the Northern Territory of Australia, in whom a diagnosis of leprosy was either known or strongly suspected. Sixty-eight biopsy samples were from 19 patients known to have leprosy, and who were under assessment for nerve grafting, results of which have already been published. We describe here the histopathological findings in the remaining 62 patients, in whom a diagnosis of leprosy was suspected on clinical grounds, backed in many cases by abnormalities of nerve conduction. Forty-one patients (66%) had abnormal histopathological findings in the nerve biopsy sample, 19 (31%) showing definite evidence of leprosy. Several patients with enlarged peripheral nerves, in whom the biopsy findings did not confine leprosy, remain under observation; their future investigation will include lymphocyte transformation tests and testing with refined lepromin, together with repeat nerve biopsy, where ethical and feasible. The clinical and epidemiological data suggest that a previous, and perhaps self-healing, form of leprosy may account for the neurological findings.