Global Preconception and Contraception Care: Using a Life-Course Approach to Improve Health Outcomes in Lower-Resource Settings.

A life-course approach incorporating appropriate preconception and contraception care is key to achieving optimal maternal, neonatal, and child health outcomes. In low- and middle-income countries (LMIC), there is a large unmet need for contraception and an estimated 49% of pregnancies are unintended. In this article, we discuss preconception and contraception care in LMIC settings including key recommendations for content and service delivery. We discuss barriers and facilitators to contraceptive provision, discuss considerations for providers who may practice in LMIC settings, and highlight strategies for achieving increased contraceptive uptake including several examples of successful programs.

Comparative effectiveness of hysteroscopic and laparoscopic sterilization for women: a retrospective cohort study.

OBJECTIVE: To compare real-world effectiveness of hysteroscopic to laparoscopic sterilization. DESIGN: Retrospective cohort of Medicaid claims for hysteroscopic or laparoscopic sterilization procedures performed in California, 2008-2014. After excluding postpartum procedures, we applied log-linear (Poisson) event-history regression models for clustered person-period data, weighted for propensity to receive either sterilization procedures, and adjusted for sociodemographic and clinical variables to examine the poststerilization pregnancy rates. SETTING: Clinics, hospitals. PATIENT(S): Women aged 18-50 years with Medicaid claims between January 1, 2008, and August 31, 2014. INTERVENTION(S): Hysteroscopic or laparoscopic sterilization procedure. MAIN OUTCOME MEASURE(S): Poststerilization pregnancy measured by pregnancy-related claims. RESULT(S): Among women with hysteroscopic (n = 5,906) or laparoscopic (n = 23,965) sterilization, poststerilization pregnancy claims were identified for 4.74% of women after hysteroscopic sterilization and 5.57% after laparoscopic sterilization. The pregnancy rates decreased over time after either procedure. Twelve months after the procedure, the crude incidence of pregnancy claims was higher for hysteroscopic sterilization than for laparoscopic sterilization (3.26 vs. 2.61 per 100 woman-years), but the propensity-weighted adjusted incidence rate ratio was 1.06 (95% confidence interval [CI], 0.85-1.26). Between 13 and 24 months after the procedure, there were fewer pregnancies for women after hysteroscopic sterilizations than for those after laparoscopic sterilizations (adjusted incidence rate ratio, 0.63 [95% CI, 0.45-0.88]), with no statistically significant differences in later years. The cumulative pregnancy rates 5 years after sterilization were lower with hysteroscopic sterilization than with laparoscopic sterilization (6.26 vs. 7.22 per 100 woman-years; propensity-weighted, adjusted risk ratio, 0.76 [95% CI, 0.62-0.90]). The poststerilization pregnancy rates varied by age and race/ethnicity. CONCLUSION(S): The pregnancy rates after female sterilization are higher than expected, whether performed hysteroscopically or laparoscopically. These findings are reassuring that the effectiveness of hysteroscopic sterilization was not inferior to laparoscopic sterilization. CLINICAL TRIAL REGISTRATION NUMBER: NCT03438682.

Patient-Centered Safety Outcomes After Hysteroscopic Compared With Laparoscopic Sterilization.

OBJECTIVE: To evaluate the real-world safety of hysteroscopic compared with laparoscopic surgical sterilization. METHODS: We conducted a retrospective cohort study of Medicaid claims for hysteroscopic or laparoscopic sterilization procedures performed in California, 2008-2014, among women aged 18-50 years. After excluding postpartum procedures, we applied log-linear (Poisson) event-history regression models for clustered person-period data, weighted for propensity to receive either sterilization procedures, and adjusted for sociodemographic and clinical characteristics that may affect outcomes of interest to patients and physicians. We assessed the following outcomes: procedural complications, additional surgical procedures (eg, hysterectomy), repeat sterilization procedures, pelvic pain, pelvic inflammatory disease (PID), abdominal pain, nonabdominal pain, and abnormal uterine bleeding. RESULTS: We identified 5,906 women who had undergone hysteroscopic and 23,965 who had undergone laparoscopic sterilization. After adjusting for sociodemographic and health history, women who had hysteroscopic sterilization were less likely to have claims for procedural complications (eg, transfusion, P<.001) on the day of surgical sterilization and additional surgical procedures (eg, hysterectomy, P=.002 at day 2-3 months postprocedure) than laparoscopic sterilization. Claims for a repeat attempt at sterilization were more common after hysteroscopic sterilization within 1 year (adjusted incident rate ratio 3.48, 95% CI 2.69-4.27) and within 5 years (adjusted incident rate ratio 2.32, 95% CI 1.84-2.79) than laparoscopic sterilization. Claims for pelvic pain (adjusted incident rate ratio 0.77, 95% CI 0.65-0.92 at 2 years), abdominal pain (adjusted incident rate ratio 0.80, 95% CI 0.68-0.93 at 7-12 months), and PID (adjusted incident rate ratio 0.55, 95% CI 0.33-0.93 at 2 years) were less common after hysteroscopic than laparoscopic sterilization. Although abnormal uterine bleeding claims were more common after hysteroscopic than laparoscopic sterilization up to 12 months postprocedure (adjusted incident rate ratio 1.37, 95% CI 1.06-1.77 at 7-12 months), there were no significant differences between methods 1 year after the procedure. CONCLUSION: Compared with laparoscopic sterilization, hysteroscopic sterilization was followed by more claims for repeat sterilization procedures and abnormal uterine bleeding, but fewer procedural complications and fewer claims for pelvic or abdominal pain. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03438682.

Comparative Effectiveness and Safety of Intrauterine Contraception and Tubal Ligation.

BACKGROUND: Tubal ligation remains common in the USA, especially among low-income patients. OBJECTIVE: To compare the effectiveness and safety of intrauterine contraceptives (IUC) to laparoscopic tubal ligation for Medicaid clients. DESIGN: We partnered with patient and clinician stakeholders to conduct a retrospective cohort study using California Medicaid claims for patients who had an IUC placed or laparoscopic tubal ligation performed in 2008-2014, excluding procedures performed within 42 days of a birth. We applied log-linear (Poisson) event-history regression models for clustered person-period data to adjust for sociodemographic variables and pre-procedure health status when examining associations between these contraceptive procedures and claims related to contraceptive failure, complications, and pain in the first year post-procedure. KEY RESULTS: We identified 35,705 patients who had a levonorgestrel IUC placed, 23,628 patients who had a copper IUC placed, and 23,965 patients who underwent laparoscopic tubal ligation. In unadjusted analyses, rates of pregnancy within 1 year were similar following levonorgestrel IUC (2.40%) or copper IUC placement (2.99%) or tubal ligation (2.64%). In adjusted analyses, compared to tubal ligation, pregnancy was less common following placement of a levonorgestrel IUC (adj IRR 0.72, 95% CI 0.64-0.82) and similar with placement of a copper IUC (adj IRR 0.92, 95% CI 0.82-1.05). Procedural complications such as infection (0.35% vs. 2.91%) were significantly less common with IUC placement than tubal ligation. Claims for pelvic and abdominal pain decreased in frequency with time since all procedures; 6 to 12 months post-procedure, pelvic pain claims were less common after levonorgestrel IUC (adj IRR 0.69, 95% CI 0.65-0.73) or copper IUC placement (adj IRR 0.70, 95% CI 0.66-0.75) than tubal ligation. CONCLUSIONS: IUC appears at least as effective as laparoscopic tubal ligation at 1-year post-procedure with lower rates of infection and pelvic pain 6 to 12 months post-procedure. CLINICAL TRIAL REGISTRATION: NCT03438682.

Women's perceptions and treatment patterns related to contraception: results of a survey of US women.

OBJECTIVES: The aim of this survey was to understand US women's contraception journey from her first prescribed method to her current one including reasons for choosing and stopping/switching methods, healthcare provider relationships, and bleeding preferences. STUDY DESIGN: We administered a nationally-representative, web-based survey of US women aged 16 to 50 years currently using (N=1656) or had previously used (N=1448) prescription contraception, or who had never used it but would consider using it in the future (N=103). Statistical analyses were based on overlap formulae with sample weights adjusted to 2010 US census demographic benchmarks. RESULTS: The survey was sent to 11,906 women, and 5957 responded (50% response rate). Among qualified respondents, 3104 had experience with prescription contraception. Oral contraceptives (OC) remain the most frequently prescribed method as first or subsequent contraception. However, as women switch to their current prescription method, more chose IUD contraception. As reported by respondents, only 48% of current users received counseling on how to use specific methods, and 58% were counseled on bleeding patterns to expect, while 67% were offered counseling on potential side effects. Many of the side effects reported in this study for first and current prescription contraception were nonspecific and may be related to a nocebo effect, lack of understanding about normal bodily fluctuations, or poor compliance. Many women (34%) reported 'making their periods lighter' as a reason for using their current prescription method, and 53% would prefer to skip their monthly period altogether. CONCLUSIONS: Misperceptions about contraception are common, and prescription contraception choice can be quite complex. Clinicians can enhance patient satisfaction by providing adequate information and matching methods to women's lifestyles, reproductive choices, and pregnancy risk. IMPLICATIONS: This study provides insight into modern women's attitudes and views toward prescription contraception that may be important to clinicians and women themselves.

A randomized comparison of a novel nitinol-frame low-dose-copper intrauterine contraceptive and a copper T380S intrauterine contraceptive.

OBJECTIVE: We sought to compare VeraCept (VC175), a novel nitinol intrauterine contraceptive (IUC) with 175 square-mm of copper surface area, to a copper T380S IUC. STUDY DESIGN: We enrolled parous women into a randomized subject-blinded comparison of VC175 and a copper T380S in a 2:1 fashion at a single clinic. The primary outcomes were total adverse events and continuation at 12 months. We also examined pain on insertion, ease of placement, expulsion, tolerability and pregnancy. Subjective ratings were on a 5-point Likert scale (0, no pain to 5, worst pain). We followed subjects through 24-month follow-up. RESULTS: We enrolled 300 women with 199 randomized to VC175 and 101 to the T380S. Insertion was successful in 198 subjects for VC175 and 100 for the T380S. Mean age was 25 years (range 18, 41), and median parity was 2 (range 1, 8), with 39% having only had Cesarean deliveries. No subjects developed clinical infection or reported serious adverse events. In the VC175 and T380S groups, mean pain at insertion was 1.4 and 2.4, respectively (p<.01). At the 12-month primary endpoint for VC175 and T380S, respectively, continuation was 84% and 68% (p<.002) with expulsions in 5.0% and 12.0% (p<.05) and removal for pain/bleeding in 3.5% and 17.0% (p<.01). At the 24-month visit for VC175 and T380S, respectively, continuation was 77% and 62% (p<.02 by log-rank). One ectopic pregnancy was identified at the 12-month follow-up in a VC175 user. No other pregnancies were diagnosed. With 297.3 and 132.4 woman-years, pregnancy rates were 0.3 and 0.0 per 100 woman-years for VC175 and T380S, respectively. CONCLUSIONS: VC175 resulted in less pain at insertion, fewer expulsions and higher total continuation than the T380S, with similar contraceptive efficacy. IMPLICATIONS: VC175 is a promising new intrauterine copper contraceptive on a nitinol frame that warrants further clinical trials.

Providing antenatal corticosteroids for preterm birth: a quality improvement initiative in Cambodia and the Philippines.

OBJECTIVE: To determine whether a simple quality improvement initiative consisting of a technical update and regular audit and feedback sessions will result in increased use of antenatal corticosteroids among pregnant women at risk of imminent preterm birth delivering at health facilities in the Philippines and Cambodia. DESIGN: Non-randomized, observational study using a pre-/post-intervention design conducted between October 2013 and June 2014. SETTING: A total of 12 high volume facilities providing Emergency Obstetric and Newborn Care services in Cambodia (6) and Philippines (6). INTERVENTION: A technical update on preterm birth and use of antenatal corticosteroids, followed by monthly audit and feedback sessions. MAIN OUTCOME MEASURE: The proportion of women at risk of imminent preterm birth who received at least one dose of dexamethasone. RESULTS: Coverage of at least one dose of dexamethasone increased from 35% at baseline to 86% at endline in Cambodia (P < 0.0001) and from 34% at baseline to 56% at endline in the Philippines (P < 0.0001), among women who had births at 24-36 weeks. In both settings baseline coverage and magnitude of improvement varied notably by facility. Availability of dexamethasone, knowledge of use and cost were not major barriers to coverage. CONCLUSIONS: A simple quality improvement strategy was feasible and effective in increasing use of dexamethasone in the management of preterm birth in 12 hospitals in Cambodia and Philippines.

Pregnancy-induced HLA antibodies respond more vigorously after renal transplantation than antibodies induced by prior transplantation.

Acute antibody mediated rejection after HLA-specific antibody incompatible renal transplantation is related to donor specific HLA antibody (DSA) levels. DSA levels may rise sharply after transplant, and aim of this study was to examine changes in DSA levels, particularly according to the primary sensitising event. Changes in 220 HLA specificities in 64 patients over the first 30days after transplantation were evaluated using microbead assays. The greatest increase from pre-treatment to peak DSA levels was seen in pregnancy-stimulated specificities, median (IQR) increase in MFI of 1981 (94-5870). The next highest increase was for those sensitised by transplant with repeat HLA epitope mismatch, at 546 (-308-2698) (p<0.01). The difference was especially marked when the pre-treatment antibody level was low; with pre-treatment MFI <1000, peak level was >1000 in 19/26 (73%) of pregnancy stimulated specificities, compared with 9/29 (31%) for all others (p<0.001). DSA production to specificities stimulated by previous pregnancy was marked, even from very low pre-transplant levels. By contrast, there was a lower rate of antibody resynthesis to specificities repeated from previous transplants, both at antigen and epitope levels.

Increasing LARC utilization: any woman, any place, any time.

Intrauterine contraceptive devices and the progestin implant are the most effective long-acting reversible contraception (LARC) methods available for preventing unintended pregnancy. LARC devices are safe, non-user-dependent methods that have the highest rates of continuation and satisfaction of all reversible contraceptives. Use of these contraceptives remains low in the United States due to several barriers including: misperceptions among both providers and patients; cost barriers; and patient access to the devices. Increasing the opportunities for women to access LARC methods in the primary care, postabortion, and postpartum setting can be achieved by addressing the system, provider, and patient barriers that exist.

Human leukocyte antigen antibody-incompatible renal transplantation: excellent medium-term outcomes with negative cytotoxic crossmatch.

BACKGROUND: Human leukocyte antigen (HLA) antibody-incompatible renal transplantation has been increasingly performed since 2000 but with few data on the medium-term outcomes. METHODS: Between 2003 and 2011, 84 patients received renal transplants with a pretreatment donor-specific antibody (DSA) level of more than 500 in a microbead assay. Seventeen patients had positive complement-dependent cytotoxic (CDC) crossmatch (XM), 44 had negative CDC XM and positive flow cytometric XM, and 23 had DSA detectable by microbead only. We also reviewed 28 patients with HLA antibodies but no DSA at transplant. DSAs were removed with plasmapheresis pretransplant, and patients did not routinely receive antithymocyte globulin posttransplant. RESULTS: Mean follow-up posttransplantation was 39.6 (range 2-91) months. Patient survival after the first year was 93.8%. Death-censored graft survival at 1, 3, and 5 years was 97.5%, 94.2%, and 80.4%, respectively, in all DSA+ve patients, worse at 5 years in the CDC+ve than in the CDC-ve/DSA+ve group at 45.6% and 88.6%, respectively (P<0.03). Five-year graft survival in the DSA-ve group was 82.1%. Rejection occurred in 53.1% of DSA+ve patients in the first year compared with 22% in the DSA-ve patients (P<0.003). CONCLUSIONS: HLA antibody-incompatible renal transplantation had a high success rate if the CDC XM was negative. Further work is required to predict which CDC+ve XM grafts will be successful and to treat slowly progressive graft damage because of DSA in the first few years after transplantation.

Double filtration plasmapheresis in antibody-incompatible kidney transplantation.

Double filtration plasmapheresis (DFPP) was used in preference to plasma exchange in our program of antibody-incompatible transplantation, to treat higher volumes of plasma. Forty-two patients had 259 sessions of DFPP, 201 pre-transplant and 58 post-transplant. At the first treatment session, the mean plasma volume treated was 3.81 L (range 3-6 L), 55.5 mL/kg (range 36.2-83.6 mL/kg). Serum IgG fell by mean 59.4% (SD 10.2%), and IgM by 69.3% (SD 16.1%). Nine patients did not require increases in plasma volumes treated, and six did not tolerate higher plasma volumes. In the remaining patients, the mean maximum plasma volume treated pre-transplant was 6.67 L (range 4-15 L), 96.1 mL/kg (range 60.2-208.9 mL/kg). The complement dependent cytotoxic crossmatch was positive in 14 cases pre-treatment, and remained positive in six (42.8%) cases. The flow cytometric crossmatch was positive in 29 cases pre-treatment, and in 21 (72.4%) after DFPP. Post-transplant, DFPP was ineffective at reducing donor specific antibody levels during periods of rapid donor specific antibody synthesis. Post-transplant, the one year graft survival rate was 94%, although there was a high rate of early rejection. In summary, DFPP enabled the treatment of plasma volumes that were almost double those that would have been feasible with plasma exchange. Despite this, most patients were transplanted with a positive crossmatch, and DFPP post-transplant was unable to control rising antibody levels.

Rises and falls in donor-specific and third-party HLA antibody levels after antibody incompatible transplantation.

BACKGROUND: After human leukocyte antigen (HLA) antibody-incompatible transplantation, donor specific and third party HLA antibodies may be found, and their levels fall in a donor-specific manner during the first month. However, these changes have not been previously described in detail. METHODS: Donor-specific HLA antibody (DSA) and third-party HLA antibody (TPA) levels were measured using the microbead method in 44 presensitized patients who had renal transplantation. RESULTS: DSA+TPA fell in the first 4 days after transplantation, and greater falls in DSA indicated absorption by the graft. This occurred for class I (57.8% fall compared with 20.2% for TPA, P<0.0005), HLA DR (63.0% vs. 24.3%, P<0.0004), and for HLA DP/DQ/DRB3-4 (34% vs. 17.5%, P=0.014). Peak DSA levels occurred at a mean of 13 days posttransplant, and they were higher than pretreatment in 25 (57%) patients and lower in 19 (43%) patients (P=ns). The risk of rejection was associated with peak DSA levels; 15 of 25 (60%) patients with DSA at median fluorescence intensity (MFI) more than 7000U experienced rejection, compared with 4 of 7 (57%) patients with peak DSA MFI 2000 to 7000U, and 2 of 12 (17%) patients with peak DSA MFI less than 2000U (P<0.02). DSA levels subsequently fell in a donor specific manner compared to TPA. CONCLUSION: DSA levels may change markedly in the first month after antibody incompatible transplantation, and the risk of rejection was associated with higher pretreatment and peak levels.

Multidimensional en-face OCT imaging of the retina.

Fast T-scanning (transverse scanning, en-face) was used to build B-scan or C-scan optical coherence tomography (OCT) images of the retina. Several unique signature patterns of en-face (coronal) are reviewed in conjunction with associated confocal images of the fundus and B-scan OCT images. Benefits in combining T-scan OCT with confocal imaging to generate pairs of OCT and confocal images similar to those generated by scanning laser ophthalmoscopy (SLO) are discussed in comparison with the spectral OCT systems. The multichannel potential of the OCT/SLO system is demonstrated with the addition of a third hardware channel which acquires and generates indocyanine green (ICG) fluorescence images. The OCT, confocal SLO and ICG fluorescence images are simultaneously presented in a two or a three screen format. A fourth channel which displays a live mix of frames of the ICG sequence superimposed on the corresponding coronal OCT slices for immediate multidimensional comparison, is also included. OSA ISP software is employed to illustrate the synergy between the simultaneously provided perspectives. This synergy promotes interpretation of information by enhancing diagnostic comparisons and facilitates internal correction of movement artifacts within C-scan and B-scan OCT images using information provided by the SLO channel.

Simultaneous OCT/SLO/ICG imaging.

PURPOSE: To evaluate how information from combined coronal optical coherence tomography (OCT) and confocal laser scanning ophthalmoscopy (SLO) with integrated simultaneous indocyanine green (ICG) dye angiography can be used in the diagnosis of a variety of macular diseases. METHODS: A compact chin-rest-based OCT/confocal imaging system was used to produce the OCT image and excite the fluorescence in the ICG dye. The same eye fundus area can be visualized with coronal (C-scans, en face) OCT and ICG angiography simultaneously. Fast T scanning (transverse scanning, en face) was used to build B- or C-scan OCT images along with confocal SLO views, with and without ICG filtration. The OCT, confocal SLO and ICG fluorescence images were simultaneously presented in a three-screen format. A live mixing channel overlaid the ICG sequence on the coronal OCT slices in a fourth panel for immediate comparison. RESULTS: Thirty eyes were imaged. The pathologic conditions studied included classic and occult neovascular membranes, vascularized RPE detachments, polypoidal choroidal vasculopathy, traumatic choroidal rupture, diabetic maculopathy, central serous retinopathy, and macular drusen. Images were evaluated with special attention toward identifying novel relationships between morphology and function revealed by the superimposition of the studies. CONCLUSIONS: Simultaneous visualization of an en face (coronal, C-scan) OCT image and of an ICG angiogram, displayed side by side and superimposed, permits more precise correlations between late fluorescence accumulation with structures deep to the retinal surface at the retina-choroid interface. The multiplanar scanning also permits immediate B-scan OCT cross-sectional views of regions of abnormal fluorescence. The paper demonstrates the synergy between the two types of studies, functional and anatomic, in providing a more complete view of the pathologic condition.

Application of flow cytometry to monitor antibody levels in ABO incompatible kidney transplantation.

Current methods of measuring ABO antibody levels based on the hemagglutination (HA) titers have the disadvantages of relatively poor reproducibility and do not offer fine discrimination of antibody concentration. We therefore developed a simple and rapid method of measuring ABO antibody levels using flow cytometry (FC). For validation, we analyzed plasma samples from 79 blood donors. Both IgM and IgG were detected and measured with IgG essentially restricted blood group O donors. Forty-two successive samples were collected from a patient with blood group O undergoing antibody removal and subsequent transplantation from a group A2 donor and tested by both HA and FC. Changes in IgG measured by FC (relative median fluorescence) correlated well with HA titers and importantly rejection episodes were preempted by a rising relative median fluorescence. The method allowed quantitative discrimination in the range of antibody levels relevant to ABO incompatible transplantation and has the advantages over HA of objective measurement and reproducibility.

New choices for patients needing kidney transplantation across antibody barriers.

Antibodies in the blood of a kidney transplant recipient can provide a barrier to transplantation, which is additional to the usual possibility of cellular rejection. The antibodies most frequently encountered are ABO (blood group) and human leucocyte antigen (HLA) (tissue-type) antibodies. About 250 living donor transplants each year in the United Kingdom have been stopped because of an antibody barrier. It is now possible to offer a choice of treatment modalities to these people, including exchange transplantation and antibody-incompatible transplantation. It is likely that both schemes will complement each other and both are available in the United Kingdom.

Blood levels of donor-specific human leukocyte antigen antibodies after renal transplantation: resolution of rejection in the presence of circulating donor-specific antibody.

BACKGROUND: Accommodation to antibody is an important mechanism in successful ABO-incompatible transplantation, but its importance in human leukocyte antigen (HLA) antibody-incompatible transplantation is less clear, as sensitive techniques facilitating daily measurement of donor-specific HLA antibodies (DSAs) have only recently been developed. METHODS: We report 24 patients who had HLA antibody-incompatible kidney transplantation (21 living donors, 3 deceased), 21 of whom had pretransplant plasmapheresis. Eight had positive complement-dependent cytotoxic (CDC) crossmatch (XM) pretransplant plasmapheresis, nine had positive flow cytometric (FC) XM, and seven had DSA detectable by microbead analysis only. After transplant, DSA levels were monitored closely with microbead assays. RESULTS: Rejection occurred in five of eight (62.5%) CDC-positive cases, in three of nine (33%) FC-positive cases, and in two of seven (29%) of microbead-only cases at a median of 6.5 days after transplantation. Resolution occurred at a median of 15 days after transplantation, in 8 of 10 cases when the microbead level of DSA had median fluorescence intensity (MFI) >2000 U, in 6 of 10 when the microbead MFI >4000 U. In 8 of 10 cases, the microbead MFI at the time of resolution was greater than at the onset. DSA did not always cause clinical rejection. In five cases with a posttransplant DSA peaking at MFI >2000 U on microbead assay, rejection did not occur. CONCLUSION: These data suggest that the dominant method of successful transplantation was function of the transplant in the presence of circulating DSA, and they also define the period during which this occurred.

Association of fulminant non-A non-B hepatitis with homozygosity for HLA A1-B8-DR3.

BACKGROUND: For the majority of cases of acute liver failure in western Europe and North America an etiology cannot be defined. The condition is most often called fulminant non-A, non-B (NANB) hepatitis. Features such as female preponderance and presence of serum autoantibodies suggest a possible autoimmune basis. The aim of the present paper was to examine a possible human leukocyte antigen (HLA) association with fulminant NANB hepatitis. METHODS: HLA A, B, and DR data of 55 adult Caucasian fulminant NANB patients were compared with those of 1449 local Caucasian controls. RESULTS: In Caucasian patients, homozygosity (but not heterozygosity) for the alleles A1, B8, and DR3 were associated with fulminant NANB hepatitis (Pcorrected = 0.02, <0.00001 and 0.002, respectively). Greatest relative risk (RR) was associated with homozygosity for the A1-B8-DR3 haplotype (P < 0.00001; RR: 12.8; 95% confidence interval [CI]: 5.7-22.3). HLA DR8 was also associated with development of the syndrome (RR: 4.2; 95%CI: 1.6-9.2). CONCLUSIONS: Homozygosity for the HLA haplotype A1-B8-DR3 confers susceptibility to the development of fulminant NANB hepatitis. This observation may imply a role for the immune response genes (which are flanked by HLA B and DR) in the pathogenesis of this syndrome.

Fiber-optic-based absolute displacement sensors at 1500 nm by means of a variant of channeled spectrum signal recovery.

An absolute displacement-sensing system based on channeled spectrum processing capable of simultaneous interrogation of fiber Bragg gratings and fiber-optic interferometric sensors is presented in which the role of the optical spectrometer is performed by a scanning Fabry-Perot filter. We demonstrate a resolution of +/-50 nm with an estimated dynamic range of 1 part in 10(5).