Enhanced recovery after fetal spina bifida surgery: what is our global practice?

OBJECTIVE: Prenatal spina bifida closure results in improved outcomes for the child compared to postnatal surgery but is associated with significant maternal morbidity. Optimization of the perioperative care for women who underwent fetal spina bifida surgery could improve maternal and pregnancy outcomes. Enhanced Recovery After Surgery (ERAS) protocols are multimodal, evidence-based care plans that have been adopted for multiple surgical procedures to promote faster and better patient recovery and shorter hospitalization. This study aims to explore if fetal centers have implemented ERAS principles in this setting. Furthermore, we provide recommendations for the perioperative management of patients undergoing fetal spina bifida surgery. METHODS: Fifty-three fetal therapy centers offering prenatal surgery for open spina bifida were identified and invited to complete a digital questionnaire covering their pre-, intra- and postoperative management. An overall score was calculated per center based on the center's compliance with 20 key ERAS principles, extrapolated from ERAS guidelines for cesarean section, gynecologic oncology and colorectal surgery. Each item was scored 1 or 0 when the center did or did not comply with each principle, with a maximum score of 20. RESULTS: The questionnaire was completed by 46 centers in 17 countries (response rate 87%). Twenty-two centers (48%) exclusively perform open fetal surgery (laparotomy and hysterotomy), whereas 14 (30%) offer both open and fetoscopic procedures and 10 (22%) use fetoscopy only. The perioperative management of patients undergoing fetoscopic and open surgery was highly similar. The median ERAS score was 12 (mean 12.5, SD 2.4, range 8-17). Center compliance was the highest for the use of regional anesthesia (98%), avoidance of bowel preparation (96%), and thromboprophylaxis (96%), while the lowest compliance was achieved for preoperative carbohydrate loading (15%), postoperative nausea and vomiting prevention (33%), avoidance of overnight fasting (33%) and a 2-hour fasting period for clear fluids (20%). ERAS scores were similar in centers with a short (2-5 days), medium (6-10 days) and long (≥11 days) hospital stay (12.8 ± 2.4, 12.1 ± 2.0, and 10.3 ± 3.2, respectively, p=0.15). Furthermore, there was no significant association between ERAS score and surgical technique or center volume. CONCLUSION: The perioperative management of fetal spina bifida surgery is highly variable across fetal therapy centers worldwide. Standardizing protocols according to ERAS principles may improve patient recovery, reduce maternal morbidity, and shorten hospital stay after fetal spina bifida surgery. This article is protected by copyright. All rights reserved.

Molecular testing of 163 patients with Morquio A (Mucopolysaccharidosis IVA) identifies 39 novel GALNS mutations.

Morquio A (Mucopolysaccharidosis IVA; MPS IVA) is an autosomal recessive lysosomal storage disorder caused by partial or total deficiency of the enzyme galactosamine-6-sulfate sulfatase (GALNS; also known as N-acetylgalactosamine-6-sulfate sulfatase) encoded by the GALNS gene. Patients who inherit two mutated GALNS gene alleles have a decreased ability to degrade the glycosaminoglycans (GAGs) keratan sulfate and chondroitin 6-sulfate, thereby causing GAG accumulation within lysosomes and consequently pleiotropic disease. GALNS mutations occur throughout the gene and many mutations are identified only in single patients or families, causing difficulties both in mutation detection and interpretation. In this study, molecular analysis of 163 patients with Morquio A identified 99 unique mutations in the GALNS gene believed to negatively impact GALNS protein function, of which 39 are previously unpublished, together with 26 single-nucleotide polymorphisms. Recommendations for the molecular testing of patients, clear reporting of sequence findings, and interpretation of sequencing data are provided.

The consequences of rheumatoid arthritis: quality of life measures in the individual patient.

Despite conventional treatment, RA still has many deleterious consequences. From the patients' perspective, these include persistent pain, functional disability, fatigue, and depression modified by health beliefs and underlying psychological problems. Disability is a consequence of pain, active synovitis and joint damage. It is usually assessed by self-reported questionnaire; the Health Assessment Questionnaire (HAQ) remains the dominant disability measure, although generic health measures such as Short Form-36 and Nottingham Health Profile provide similar information. Treatment with disease modifying drugs and biologic agents improves pain, fatigue and disability. We specifically evaluated the effects of both these drugs and also disease duration on disability assessed by HAQ scores, as there is most information on this topic and it is of fundamental importance to patients. In early RA HAQ gives a 'J-shaped' curve; the initial fall is due to the immediate benefits of treatment and the subsequent gradual rise due to the inability of therapy to fully suppress the disease or prevent progressive joint damage. In established RA HAQ scores increase by about 1% annually and over 25 years average HAQ scores increase by 1.0. Disease modifying drugs and biologics both significantly reduce HAQ scores and the reduction is maintained for 2-5 years. This reduction is seen in both early and established disease. Early steroid therapy has immediate symptomatic treatment, but does not have long-term benefits. Over 5 years the impact of aggressive therapy with disease modifying drugs declines and there is evidence that insufficient treatment is given to many patients with RA. The outcome of RA is greatly improved by current treatment with disease modifying drugs and biologic agents. However, more needs to be done and achieving better results is enhanced by routinely measuring the impact of the disease in routine practice.

Radioelectrocomplexing: a counterelectrophoretic method for hapten--antibody interaction.

We have described an application of a radioimmunoassay (RIA)method, known as radioelectrocomplexing (REC), which involves the anodal migration of antigen and the cathodal migration of antibody in agar electrophoresis. The agar is divided into zones of free antigen (DNP125I-HSA) and antigen bound with anti-DNP. Complete assays of anti-DNP can be performed in 2-4 hr since both immune complex formation and separation of free from bound antigen can be accomplished by electrophoresis in 60-90 min. Estimation of the weight of specifically-purified anti-DNP chicken antibodies in the nanogram range by REC is of the same order as the reported sensitivity of other RIA methods. The method was capable of demonstrating the higher avidity of the 17 S than 7 S antibody. Based on hapten inhibition the relative binding constants of DNP derivatives and anti-DNP were of the same order as reported from more definitive methods.

Reducing missed opportunities for immunizations. Easier said than done.

BACKGROUND: Missed opportunities for immunizations are associated with underimmunization of preschool-age children. Practice policies limiting immunizations to scheduled preventive visits and guidelines requiring legal guardians to sign consent forms for vaccinations are 2 factors contributing to missed opportunities. However, methods to change these policies have not been sufficiently evaluated. OBJECTIVE: To measure the effectiveness of (1) changing practice policies to incorporate the new national standard to screen and vaccinate eligible children at all office visits and (2) eliminating legal guardian signature requirements. DESIGN: A randomized controlled trial of 2 interventions: (1) changing practice policy and routine to have office nurses screen for immunization status at all visits, attach immunization reminder cards to medical charts for eligible patients, and have providers vaccinate eligible children ("no missed opportunities" intervention) and (2) changing practice guidelines to allow vaccinations without a legal guardian's signature. The first intervention was performed at both sites; the second only at the neighborhood health center (NHC). SETTING: A Pediatric Continuity Clinic in a teaching hospital (hereafter referred to as Clinic), and an NHC. PATIENTS: Enrolled in the trial were 1005 Clinic patients and 983 NHC patients, 0 to 2 years of age. MAIN OUTCOME MEASURES: Missed opportunity rates, immunization rates, and rates of preventive services. RESULTS: Eliminating the requirement for a legal guardian's signature had no effect on any of the outcome measures. The no missed opportunities intervention was partially effective. Study patients had slightly fewer missed opportunities than control patients at each site: (0.60 vs 0.90 per patient per year at the Clinic, P = .01; 1.1 vs 1.3 per patient per year at the NHC, P = .02). For study group patients, immunization reminder cards were attached to medical charts in only one third of vaccine-eligible visits; when attached, they markedly increased vaccination by providers (odds ratio for vaccinating at a visit was 6.9 comparing visits when immunization reminder cards were attached vs not attached). However, at the end of the study, immunization rates were similar for study and control groups at each site. The number of undervaccinated days was slightly lower for the no missed opportunities study group at the Clinic than for the control group (56 days vs 77 days, P < .001), but they were similar for both groups at the NHC. There were no differences in rates of preventive visits or screening tests between study and control groups. CONCLUSIONS: The interventions evaluated to reduce missed opportunities did not increase immunization rates. The key problem was failure to screen for immunization status at all visits. More effective interventions will be needed to overcome barriers within busy primary care practices to substantially reduce missed opportunities.

The 5-HT3 antagonist, BRL 43694, does not compromise the efficacy of cisplatin in tumour-bearing mice.

Binary combinations of cisplatin and the 5-HT3 antagonist, BRL 43694, have been used to treat both conventional mice bearing either L1210 leukaemia or ADJ/PC6 plasmacytoma and nude mice xenografted with a human ovarian carcinoma (HX/110). In no case was there evidence for antagonism by the antiemetic of the antitumour properties of cisplatin.

Sequence-dependent activity of 5-fluorouracil plus tauromustine in a transplantable well-differentiated murine colon adenocarcinoma.

Previous in vitro studies with 5-Fluorouracil (5-FU) plus Tauromustine (TCNU) demonstrated sequence-dependent effects. This study extended these investigations into an in vivo experimental model, relevant to clinical disease. A transplantable murine adenocarcinoma of the colon, MAC 29, was shown to have stable histology and reproducible growth. This model was used to determine the influence of sequence of administration of this drug combination. Effects ranged from antagonism, with 5-FU given 24 hours before TCNU, to addition, simultaneous treatment, and synergism, 5-FU 24 hours after TCNU. Careful consideration of sequence should be made during the evaluation of this combination in clinical trials.

The Cuban immigration of 1980: a special mental health challenge.

The 124,769 Cubans who entered the United States from Cuba in a boatlift in 1980 included a small minority of people who needed mental health care. Some had been taken involuntarily from psychiatric hospitals, mental retardation facilities, jails, and prisons. The National Institute of Mental Health, Public Health Service (PHS), was responsible for mental health screening, evaluation, and treatment of the Cuban Entrants. Bilingual psychiatrists and psychologists found that many Entrants given preliminary evaluations showed evidence of transient situational stress reactions, not psychiatric illnesses. Entrants who had not yet been sponsored were consolidated into one facility in October 1980, and about 100 of those with severe problems were transferred to an Immigration and Naturalization Service-PHS evaluation facility in Washington, DC. Between March 1, 1981, and March 1, 1982, a total of 3,035 Entrants were evaluated at both facilities. Among the 1,307 persons who presented symptoms, there was a primary diagnosis of personality disorders for 26 percent, schizophrenic disorders for 15 percent, adjustment disorders for 14.5 percent, mental retardation for 8.6 percent, chronic alcohol abuse for 8.6 percent, and major depression for 7.2 percent. Only 459 Cubans with symptoms were found to be in need of further psychiatric care. As of October 1984, many Entrants with psychiatric illnesses remained under inpatient or community-based halfway house psychiatric care as a direct Federal responsibility. A PHS program for further placement in community-based facilities is underway.

A randomised, double-blind, placebo-controlled trial of a recombinant version of human alpha-fetoprotein (MM-093) in patients with active rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) tends to remit during pregnancy, with more patients achieving remission in the third trimester, coinciding with an increase in levels of alpha-fetoprotein (AFP). In vitro and animal studies have shown that AFP has immunomodulatory properties. MM-093 is a non-glycosylated, recombinant version of human AFP. OBJECTIVE: To assess the safety, tolerability and clinical effects of MM-093 during a 12-week, randomised, double-blind, placebo-controlled study. METHODS: 12 patients with RA, who had active disease and were on stable doses of methotrexate, received weekly subcutaneous injections of placebo or 21 mg of MM-093. Assessments were carried out at baseline and weekly thereafter. RESULTS: Baseline characteristics were similar in both groups. There was one dropout in the placebo group, due to flare of disease. Treatment with MM-093 was well tolerated. No serious adverse event was observed. By day 85, MM-093 produced a significant mean improvement from baseline in Disease Activity Score 28 (DAS28; 0.913 vs 0.008, p = 0.033) and patient's global assessment (28.9% vs -36.3%, p = 0.02) compared with placebo. CONCLUSION: This is the first randomised, controlled trial of MM-093, a recombinant version of human AFP, in patients with RA. MM-093 was well tolerated. Evidence of efficacy was observed, suggesting that MM-093 may have therapeutic potential in RA.

Fatigue in rheumatoid arthritis reflects pain, not disease activity.

OBJECTIVE: We determined the amount of fatigue experienced by patients with RA, and its relationship to synovitis, pain and other common clinical features. We also examined to what extent RA fatigue is improved by disease-modifying antirheumatic drugs (DMARDs) and anti-tumour necrosis factor (TNF) therapy. METHODS: We studied two cohorts of 238 and 274 RA patients cross-sectionally and examined treatment responses in 30 RA patients starting anti-TNF and 54 starting DMARDs followed for 3 and 6 months. We measured fatigue using visual analogue scores (VAS) and Medical Outcomes Study Short Form 36 (SF-36) vitality scores. We recorded the disease activity score for 28 joints and its components (tender/swollen joint counts, patient global assessment, ESR), morning stiffness, health assessment questionnaire, physician global assessment, erosive disease, nodules, rheumatoid factor, concomitant medications and illnesses, and the SF-36 questionnaire. RESULTS: Fatigue was common in RA patients; over 80% had clinically relevant fatigue (VAS > or =20 mm), over 50% had high levels (VAS > or =50 mm). It was associated with pain and changes in mental health, particularly depression. In each of the two cross-sectional cohorts, this relationship was similar whichever measures of fatigue and mental health were used. Fatigue fell with DMARDs and anti-TNF: before treatment, 87% of patients had high fatigue, after treatment this fell to 50%. These treatment effects were mainly linked to improvements in pain. CONCLUSIONS: High fatigue levels characterize RA and are mainly linked to pain and depression. The association with disease activity is secondary. Fatigue falls with DMARD and anti-TNF therapy. The balance of evidence suggests that fatigue is centrally mediated in established RA.

Carcinoid infiltration and fibroplastic changes of the mesentery as a cause of malabsorption.

The presentation of carcinoid involvement of the mesentery is described, with clinical manifestation of severe malabsorption: angiographically it resembled retractile mesenteritis. The special biologic activity of the carcinoid cells inducing fibroblastic activity with secondary alterations of vascular, lymphatic and neural structures of the mesentery is discussed in relation to the altered physiology and morphology of the intestine, causing the clinical picture of sprue.

Male postpubertal facial growth in Class II malocclusions.

Maxillary and mandibular postpubertal growth changes were assessed from lateral cephalograms taken when subjects were 16 and 20 years of age. The sample consisted of 39 male subjects with no previous orthodontic treatment who exhibited Class II skeletal characteristics. Significant increases in mean maxillary and mandibular measurements were observed over the age period studied. Mean mandibular growth (Co-Gn) was approximately three times that of maxillary growth (Co-A). Total mandibular growth observed between 16 to 20 years of age was approximately 4.3 mm. The mandible appeared to rotate anteriorly superiorly, reflected by a mean reduction in mandibular plane angle of 1.47 degrees and a greater increase in posterior versus anterior face height. There were not statistically significant changes in incisor angulation. Mean growth changes in this Class II sample were comparable to those previously reported for male subjects with Class I malocclusions over the same age period, suggesting a similarity in postpubertal development between these two groups.

Tolerability and reasons for discontinuation of Norplant in an inner city population.

We carried out a retrospective analysis of the continuation rates of 142 Norplant acceptors. Follow-up data was available on 110. We assessed the relative impact of side effects on discontinuation. No serious complications (immediate or late) were observed during the 3-year study period and no pregnancies occurred. The 3-year continuation rate was 88%. The commonest reported side effect was cycle disruption (64% of users). However this only accounted for 31% of discontinuations. This we attribute to thorough counselling about menstrual disruption. On the other hand androgenic side effects accounted for 12% of discontinuations but were experienced by 10% of users-perhaps because some users did not expect them. We conclude that Norplant is highly acceptable when offered with specialist counselling and support. Non-bleeding side effects accounted for relatively higher discontinuations and may need to be emphasised in counselling. A dedicated service enhanced acceptability.

Pathovar-Specific Antigens of Xanthomonas campestris pv. begoniae and X. campestris pv. pelargonii Detected with Monoclonal Antibodies.

Two monoclonal antibodies specific for lipopolysaccharide antigens of Xanthomonas campestris pv. begoniae and pv. pelargonii reacted with all of their respective pathovar strains and not with 130 strains of other xanthomonads or 89 nonxanthomonads tested. These results, as well as previous results, indicate that pathovar-specific monoclonal antibodies were readily generated to strains of X. campestris pathovars that generally infect single hosts.

Calcium metabolism in malaria-infected erythrocytes.

Changes in the concentration of free calcium regulate many intracellular metabolic pathways and other important aspects of cellular function. The erythrocyte maintains intracellular calcium concentrations within a narrow range, but infection by malarial parasites disrupts these homeostatic mechanisms. The observation that infected erythrocytes have supranormal concentrations of calcium raises questions about the storage and functions of calcium ions within parasites. These are addressed in the following review by Sanjeev Krishna and Laura Squire-Pollard.

Monoclonal antibody study of the decorated spongiome of contractile vacuole complexes of Paramecium.

A monoclonal antibody (mAb) has been developed and selected by immunofluorescence for the radial canals of the contractile vacuole complex (CVC) of Paramecium multimicronucleatum. By applying indirect immunogold labeling to thin frozen sections this mAb has been shown at the electron microscopic level to be specific for the decorated spongiome. We have used the mAb to study the normal interfission appearance as well as developmental stages of the decorated spongiomes. Two decorated spongiomes, presumably involved in water sequestration, radiate as 5-10 bands from unlabeled, circular, 25 microns diameter centers. Two new CVCs arise just anterior to the space occupied by the old spongiomes, the new anterior CVC appearing slightly before the posterior one. Development of the new spongiomes around a 10 microns unlabeled central zone is accompanied by a regression of old spongiome bands until the lengths of these bands in both old and new CVCs are equal just before cell division. After division both old and new spongiome bands grow at equal rates to the same length. Exceptions to the above general scheme, both in number of CVCs in interfission, as well as in position of the new relative to the old CVCs, are also observed.