CAnceR IN PreGnancy (CARING) - a retrospective study of cancer diagnosed during pregnancy in the United Kingdom.

BACKGROUND: The incidence of cancer diagnosed during pregnancy is increasing. Data relating to investigation and management, as well as maternal and foetal outcomes is lacking in a United Kingdom (UK) population. METHODS: In this retrospective study we report data from 119 patients diagnosed with cancer during pregnancy from 14 cancer centres in the UK across a five-year period (2016-2020). RESULTS: Median age at diagnosis was 33 years, with breast, skin and haematological the most common primary sites. The majority of cases were new diagnoses (109 patients, 91.6%). Most patients were treated with radical intent (96 patients, 80.7%), however, gastrointestinal cancers were associated with a high rate of palliative intent treatment (63.6%). Intervention was commenced during pregnancy in 68 (57.1%) patients; 44 (37%) had surgery and 31 (26.1%) received chemotherapy. Live births occurred in 98 (81.7%) of the cases, with 54 (55.1%) of these delivered by caesarean section. Maternal mortality during the study period was 20.2%. CONCLUSIONS: This is the first pan-tumour report of diagnosis, management and outcomes of cancer diagnosed during pregnancy in the UK. Our findings demonstrate proof of concept that data collection is feasible and highlight the need for further research in this cohort of patients.

Auditory nerve responses to monophasic and biphasic electric stimuli.

Charge-balanced, biphasic stimulus pulses are commonly used in implantable cochlear prostheses as they can be safely delivered to living tissue. However, monophasic stimuli are more efficient (i.e. producing lower thresholds) and likely provide more spatially selective excitation of nerve fibers. We examined the neural responses to monophasic, 'pseudomonophasic', and biphasic stimuli to better understand the inherent tradeoffs of these stimuli. Using guinea pig and cat animal models, we compared the auditory nerve responses to both 40 micros monophasic and 40 micros/phase biphasic stimuli using both electrically evoked compound action potential and single-fiber recordings. We also made comparisons using a computational model of the feline auditory nerve fiber. In all cases, our stimuli were cathodic monophasic and cathodic-first biphasic pulses. As expected, monophasic stimuli provided lower thresholds relative to biphasic stimuli. They also evoked responses with relatively longer latencies. We also examined responses to charge-balanced biphasic pulses composed of two phases of differing duration (i.e. pseudomonophasic stimuli). The first phase was fixed at 40 micros, while the second phase was systematically varied from 40 to 4000 micros. With a relatively long second phase, we hypothesized that these stimuli would provide some of the beneficial features of monophasic stimuli. Both the gross-potential and single-fiber data confirmed this and indicate that the largest incremental effects of changing the second-phase duration occur for durations less than 500 micros. Consideration of single-fiber data and computer simulations suggest that these results are consistent with the neural membrane acting as a leaky integrator. The computer simulations also suggest that the integrative properties at least partially account for the difference between our monophasic-biphasic results and previously published data. Our results apply to cathodic-leading stimuli; due to differing patterns of membrane depolarization, they may not be applicable to situations using anodic-leading stimuli. Finally, we observed differences between the guinea pig and cat response patterns. Compared to cats, guinea pigs produced smaller monophasic vs. biphasic threshold differences. This interspecies disparity may be due to differences in cochlear anatomy.

Preparing for the future in a local public health organization.

One of the most difficult issues in strategic planning in public health organizations is how to harness the energy generated in the process of strategic thinking and focus it on strategy formulation. This article is about one local public health organization's experience in developing program priorities, building consensus about the priorities, and making operational the adaptive strategies relative to each program. The results should be useful to all public health organizations attempting to direct strategic thinking toward the formulation of practical and motivational strategies for the future.

CEO summit. The new delivery & financing realities. Part II of III.

In cooperation with McManis Associates Inc., Hospitals & Health Networks recently convened a summit on the integration of financing and delivery in health care. This is the second of a three-part series on lessons learned by those on the front lines of integration activity. The session was designed and facilitated by senior associates at McManis. Among the issues discussed in this second segment. What level of understanding do purchasers have of quality differentiators in health care services? Can provider-driven integrated delivery systems compete with insurer-driven ones? And what happens when, as in the Philadelphia market, a large integrated delivery system merges with a dominant insurer? Can that model be replicated in other markets?

CEO summit. The new delivery & financing realities. Part III of III.

In cooperation with McManis Associates Inc., Washington, Hospitals & Health Networks recently convened a summit on the integration of financing and delivery in health care. This installment is the third of a three-part series on lessons learned by those on the front lines of integration activity. The session was designed and facilitated by senior associates at McManis. Among the issues summit participants discussed in the second segment: What level of understanding do purchasers have of the factors that differentiate quality in health care services? Can provider-driven integrated delivery systems compete with insurer-driven ones? And what happens when a large integrated delivery system merges with a dominant insurer, as happened in the Philadelphia market? Can that model be successfully replicated in other markets? In this final segment, participants talk about whether providers' deep connections to their communities will add value in a reformed delivery system; how incentives might be aligned among all the players in integrated networks and organizations; how the concept of community focus might be redefined under systems integration; and the process involved in preparing for constant, accelerated change. The second segment concluded with comments about the assets providers and insurers bring to integrated health systems, and whether the merger experience of Graduate Health System and QCC/Independence Blue Cross could be replicated in other markets or not.

CEO summit. The new delivery & financing realities. Part I of III.

In cooperation with McManis Associates Inc., Hospitals & Health Networks recently convened a summit on the integration of financing and delivery of health care. This report is the first of a three-part series on lessons learned by those on the front lines of integration activity. The session was designed and facilitated by senior associates at McManis. Among the issues discussed in this first segment: Is integration necessary to satisfy the demands of health care payers? Is integration the way to cost-containment? How can costs be squeezed out of the system? What relationship will physicians have to hospitals and insurers in integrated systems?

Second-line antirheumatic drugs in the elderly with rheumatoid arthritis: a post hoc analysis of three controlled trials.

This study assessed the relative efficacy and toxicity of second-line antirheumatic drugs in patients 65 years of age or older compared to younger counterparts. The results of three prospective, double-blind, parallel, randomized, multicenter trials were reanalyzed, stratifying outcomes by intervention and patient age. Efficacy was assessed by categorizing patient responses as follows: important improvement, no meaningful change, or progressive disease. Toxicity was analyzed by comparing withdrawal rates due to adverse effects. The three trials compared the following treatments: (1) D-penicillamine 10-12 mg/day versus azathioprine 1.25-1.5 mg/kg/day; (2) gold sodium thiomalate 50 mg intramuscularly weekly versus auranofin 6 mg/day versus placebo; and (3) pulse oral methotrexate 7.5-15.0 mg weekly versus placebo. At baseline, 103 patients age 65 or older were similar to 485 patients less than 65 years of age, with the exception of disease duration in all studies and erythrocyte sedimentation rate in one study. For patients completing each study, efficacy outcomes based on age were not significantly different. Withdrawal rates due to adverse drug reactions were also not significantly different.

Methotrexate therapy in rheumatoid arthritis: 2-year retrospective followup study.

Clinical and laboratory data in 124 patients with rheumatoid arthritis treated with methotrexate (MTX) were retrospectively reviewed over the initial 2 years after the start of treatment. Clinical improvement occurred in 103 (83%) patients after 12 weeks of treatment. At 2 years of followup, 60 patients (48%) continued to receive MTX with sustained clinical benefit. It has been discontinued in 64 (52%) patients (adverse drug reactions in 38, lack of clinical benefit in 15, and miscellaneous reasons in 11). Patients with adverse drug reactions had higher initial serum creatinine and blood urea nitrogen values than patients without adverse drug reactions.

The effectiveness of smoking cessation methods for smokers in public health maternity clinics: a randomized trial.

Little insight is available in the literature on how best to assist the pregnant smoker in public health maternity clinics to quit during pregnancy. A randomized pretest/posttest experiment was used to evaluate the effectiveness of two different self-help cessation methods. Three hundred and nine pregnant women from three public health maternity clinics were assigned randomly to one of three groups with one-third assigned to each: a control group; a group receiving the American Lung Association's Freedom From Smoking Manual; and those receiving A Pregnant Woman's Self-Help Guide to Quit Smoking. Using a saliva thiocyanate (SCN) and behavioral report at mid-pregnancy and end of pregnancy to confirm cessation or reduction, 2 per cent in the control group quit and 7 per cent reduced their SCN levels substantially. Of the women assigned to the ALA method, 6 per cent quit and 14 per cent reduced their SCN levels substantially. Of the women who used the Guide, 14 per cent quit and 17 per cent reduced their SCN levels substantially. Results of this trial indicate that health education methods tailored to the pregnant smoker are more effective in changing smoking behavior than the standard clinic information and advice to quit and/or the use of smoking cessation methods not tailored to the needs of the pregnant smoker.

Chlorambucil therapy in rheumatoid arthritis: clinical experience in 28 patients and literature review.

Our clinical experience in 28 patients receiving chlorambucil for rheumatoid arthritis (RA) and the reports on chlorambucil therapy are reviewed. Our study population and other reports generally represent patients with severe RA who had either failed to improve or developed significant toxicity during previous treatment with conventional slow acting anti-rheumatic drugs (SAARDs). Seventy-two percent of patients had a significant clinical improvement during chlorambucil therapy and reports of complete remission are given, although the incidence of remission is unknown. Hematologic complications are often reported, but appeared more frequently in our experience than previously reported. Hematologic toxicity required that chlorambucil be discontinued in the majority of our cases. Two deaths from suspected drug induced malignancies are reported. Although chlorambucil appears to be effective in the control of active RA, the potential for drug induced toxicity and malignancies may outweigh the benefit of continued use of this experimental therapy in RA.

'Pseudoseptic' arthritis in patients with rheumatoid arthritis.

It is generally recognized that patients with rheumatoid arthritis are at greater risk than the general population for the development of bacterial joint infection. It is not usually appreciated, however, that such patients may present with a clinical syndrome that mimics septic arthritis in most respects except that all cultures are consistently negative and antibiotics are not essential for treatment. We report our experience with five cases of "pseudoseptic" arthritis in patients with rheumatoid arthritis and suggest an approach for management.

Comparison of low-dose oral pulse methotrexate and placebo in the treatment of rheumatoid arthritis. A controlled clinical trial.

One hundred eighty-nine patients with rheumatoid arthritis were entered into a prospective, controlled, double-blind multicenter trial comparing placebo and methotrexate (MTX). One hundred ten patients completed 18 weeks of therapy. No remissions were seen, but patients able to tolerate low-dose pulse MTX therapy were significantly improved, compared with patients receiving placebo therapy, for all clinical variables measured, including joint pain/tenderness and swelling counts, rheumatoid nodules, and patient and physician assessment of disease activity. MTX treatment demonstrated statistically significant improvement over placebo in patients with anemia, elevated erythrocyte sedimentation rate, and rheumatoid factor. However, nearly one-third of the patients receiving MTX were withdrawn for adverse drug reactions, of which elevated levels of liver enzymes was the most common. Pancytopenia occurred in 2 patients taking MTX. All adverse drug effects resolved without sequelae. MTX appears to be effective in the treatment of active rheumatoid arthritis but requires close monitoring for toxicity.

Circulating immune complexes containing secretory IgA in jejunoileal bypass disease.

Thirteen patients were studied after jejunoileal bypass (JIB) surgery. Seven developed arthritis and six did not. Circulating immune complexes containing IgG and IgA were detected in the sera of patients with and without arthritis. IgA complexes were shown to contain secretory component, a protein predominantly associated with intraluminal IgA, in significantly higher levels in patients with arthritis. Analytical ultracentrifugation showed complexes of approximately 10 X 8S, consistent with the size of secretory IgA. Arthritis after JIB appears to be associated with circulating immune complexes containing secretory IgA.

Double-blind, multicenter controlled trial comparing topical dimethyl sulfoxide and normal saline for treatment of hand ulcers in patients with systemic sclerosis.

A prospective, randomized, double-blind trial compared topical therapy with 0.85% normal saline, 2% dimethyl sulfoxide (DMSO), and 70% DMSO for treatment of digital ulcers in 84 patients with systemic sclerosis. There were no statistically significant differences among the 3 treatment groups in the improvement in the total number of open ulcers, total surface area of open ulcers, average surface area per open ulcer, number of infected ulcers, number of inflamed ulcers, or patient pain assessment. While some patients improved during the study, improvement could not be attributed to a specific treatment. Over one-quarter of the patients treated with 70% DMSO were withdrawn for significant skin toxicity.

Arthrocentesis.

Aspiration of the synovial joints is an important part of the diagnostic and therapeutic armamentarium of the physician and may provide vital information that can be obtained in no other way. As with any other technique in medicine, skill and safety in the aspiration of joints can be acquired only through careful study and continued practice in arthrocentesis. When appropriate preparations and precautions are observed, obtaining fluid from synovial joints is safe, relatively pain free, inexpensive, and extremely beneficial to the patient.

Outcome assessment in clinical trials. Evidence for the sensitivity of a health status measure.

Health status measures are conceptually relevant to the assessment of clinical outcome in the rheumatic diseases, but their ability to detect meaningful changes in health has not been clearly demonstrated. This report describes the performance of a self-administered health status questionnaire in a randomized, double-blind, 21-week comparison of placebo, oral gold, and injectable gold in rheumatoid arthritis patients. Outcome was assessed by standard clinical measures, including joint count, grip strength, and laboratory tests, and by the Arthritis Impact Measurement Scales, a reliable and valid health status measure that assesses physical disability, psychological status, and pain. Data from the clinical and health status measures produced highly similar conclusions: injectable and oral gold are more effective than placebo for rheumatoid arthritis, and injections are slightly more effective than oral gold. The health status measure was thus quite sensitive to clinically meaningful drug-induced improvements. These findings provide justification for the further application of health status measures to clinical trials of chronic disease.

Azathioprine versus D-penicillamine in rheumatoid arthritis patients who have been treated unsuccessfully with gold.

Two hundred six patients were entered into a prospective controlled, double-blind, multicenter trial comparing azathioprine (AZA) 1.25-1.5 mg/kg/day with D-penicillamine (DP) 10-12 mg/kg/day. One hundred thirty-four patients completed 24 weeks of therapy. Improvement in nearly all efficacy variables was seen in both groups. Patients taking DP demonstrated a greater rise in hemoglobin concentration and greater fall in erythrocyte sedimentation rate than patients receiving AZA; these were the only efficacy variables with a significant difference between the treatment groups. Fewer withdrawals for adverse reactions occurred among the patients receiving AZA, but the difference was not significant. Patients receiving AZA were withdrawn from the drug mainly for abnormal liver function test results, nausea and gastrointestinal upset, and leukopenia. The main reasons for withdrawal of patients receiving DP were nausea, rash and pruritus, thrombocytopenia, dysgeusia, and proteinuria.