Increasing uptake of long-acting reversible contraception with structured contraceptive counselling: cluster randomised controlled trial (the LOWE trial).

OBJECTIVE: To evaluate the effect of structured contraceptive counselling on the uptake of long-acting reversible contraceptives (LARCs) and pregnancy rates. DESIGN: Cluster randomised trial. SETTING: Abortion, youth and maternal health clinics in Stockholm, Sweden. POPULATION: Sexually active women aged ≥18 years without a wish for pregnancy seeking abortion and/or contraceptive counselling. METHODS: For participants in clinics randomised to intervention, trained healthcare providers implemented a study-specific intervention package designed for structured contraceptive counselling. Participants in the control clinics received routine counselling. MAIN OUTCOME MEASURES: The primary outcome was choice of LARCs at first visit. Secondary outcomes were LARC initiation at 3 months and pregnancy rates at 3 and 12 months. We used logistic mixed-effects models with random intercept for clinic to account for clustering. RESULTS: From September 2017 to May 2019, 28 randomised clinics enrolled 1364 participants. Analyses including 1338 subjects showed that more participants in the intervention group compared with the control group chose LARCs: 267/658 (40.6%) versus 206/680 (30.3%) (OR 2.77, 95% CI 1.99-3.86). LARC initiation was higher in the intervention group compared with the control group: 213/528 (40.3%) versus 153/531 (28.8%) (OR 1.74, 95% CI 1.22-2.49). At the abortion clinics, the pregnancy rate was significantly lower at 12 months in the intervention group compared with the control group: 13/101 (12.9%) versus 28/103 (27.2%) (OR 0.39, 95% CI 0.18-0.88). CONCLUSIONS: Structured contraceptive counselling increased LARC uptake in all clinics and significantly reduced unintended pregnancy rates in abortion clinics at the 12 months follow-up. TWEETABLE ABSTRACT: Structured contraceptive counselling increased LARC uptake and reduced pregnancy rates at 12 months.

Efficacy and safety of very early medical termination of pregnancy: a cohort study.

OBJECTIVE: To assess the efficacy and safety of medical termination of pregnancy (MTOP) when no intrauterine pregnancy (IUP) is confirmed on ultrasound. DESIGN: Retrospective case-note review. SETTING: Two gynaecological clinics in Vienna, Austria, and Gothenburg, Sweden. POPULATION: All women with gestations of ≤49 days undergoing an MTOP during 2004-14 (Vienna) and 2012-15 (Gothenburg). METHODS: Two study cohorts were created: women with and women without a confirmed IUP. An IUP was defined as the intrauterine location of a yolk sac or fetal structure visible by ultrasound. Women with an IUP were selected randomly and included in the IUP cohort. MAIN OUTCOME MEASURES: Efficacy of MTOP, defined as no continuing pregnancy and with no need of surgery for incomplete TOP. RESULTS: After excluding 11 women diagnosed with an extra-uterine or molar pregnancy, 2643 cases were included in the final analysis; 1120 (98.2%) had a successful TOP in the no-IUP group, compared with 1458 (97.1%) in the IUP group, with a risk difference of 1.09% (95% confidence interval, 95% CI, -0.14, 2.32%; P = 0.077). Significantly more women with confirmed IUP were diagnosed with incomplete TOP, and were treated with either surgery or additional medical treatment of misoprostol [64 (4.3%) versus 21 (1.8%); risk difference -2.42%; 95% CI -3.9, -1.1%; P < 0.001]. CONCLUSIONS: There was no difference between the groups in efficacy of MTOP, whereas early treatment resulted in significantly fewer interventions for incomplete TOP. The risk of ectopic pregnancy needs to be considered if treatment is initiated before an IUP is confirmed, but with structured clinical protocols the possibility of the early detection of an ectopic pregnancy in an asymptomatic phase may increase. TWEETABLE ABSTRACT: MTOP before confirmed intrauterine pregnancy is as effective as at later gestation with less incomplete TOP.

The use of clinical information in diagnosing chronic heart failure: a comparison between general practitioners, cardiologists, and students.

In a clinical judgement analysis study, 27 general practitioners, 22 cardiologists, and 21 medical students assessed 40 case vignettes with regard to the probability of heart failure, in order to study the weights of different kinds of information (cues) measured by the regression coefficients in a multiple regression model. The vignettes were based on actual patients. We found that diagnostic accomplishment and diagnostic strategies were surprisingly similar on the group level, but very different on the individual level. The most important cues for the participants were cardiac enlargement and pulmonary stasis. Strategies in which cardiac enlargement was the predominating cue led to a higher diagnostic accomplishment; a third of the participants used such strategies. The cues given in the vignettes could have been utilized more efficiently; cardiac enlargement seems to be more important and "classical" symptoms less important for predicting heart failure than the participants realize.

Factors influencing GPs' decisions on the treatment of hypercholesterolaemic patients.

OBJECTIVE: To study factors influencing GPs' decisions to prescribe lipid-lowering drugs and how their judgements agree with the Swedish guidelines on hyperlipidaemia. DESIGN: Postal questionnaire. SETTING: Primary health care. Authentic written case descriptions of patients, all with a cholesterol value of at least 5.5 mmol/l and with variations in seven other variables (cues) in a Clinical Judgement Analysis (CJA) design. SUBJECTS: Sixty randomly selected primary health care doctors in the south-eastern Stockholm area. RESULTS: Thirty-eight doctors answered the questionnaire. Coronary heart disease had the highest influence on judgements, followed by cholesterol. The majority of doctors used two or three of the eight cues. Doctors differed markedly in their strategies. One in four did not use coronary heart disease in their judgements, even though all patients with this risk factor present (12/40) should receive pharmacological treatment, according to the guidelines. Doctors who adhered to the guidelines in this respect were younger than those who did not. The GPs' insights into their own strategies were good. CONCLUSIONS: The results indicate that doctors use very different judgement strategies for drug prescription concerning patients with hypercholesterolaemia. A fairly large subgroup of the doctors did not include coronary heart disease in their judgements, in contrast to the present guidelines.

Endotoxin release from Escherichia coli after exposure to tobramycin: dose-dependency and reduction in cefuroxime-induced endotoxin release.

OBJECTIVE: To study the release of free endotoxin from Escherichia coli exposed to varying concentrations of the penicillin-binding protein (PBP) 3-specific beta-lactam antibiotic cefuroxime, the aminoglycoside tobramycin, and a combination of the two, and to test the relationship between bacterial killing rate and endotoxin release. METHODS: A clinical isolate of Escherichia coli in logarithmic phase was exposed to 0.1, 2, 10, and 50 x minimum inhibitory concentration (MIC) of cefuroxime, tobramycin, and a combination of the two. Samples for viable counts and endotoxin analysis were drawn immediately before and after the addition of the antibiotics and at 1, 2, 4, 6, and 24 h. All experiments were performed in triplicate. For the analysis of endotoxin, a chromogenic limulus amoebocyte lysate assay was used. RESULTS: Endotoxin liberation was found to be proportional to the number of killed bacteria for each antibiotic regimen at each concentration level justifying the endotoxin-liberating potential to be expressed as release of endotoxin per killed bacterium, an expression that was independent of the inoculum size. At all concentration levels there was a statistically significant difference between the treatments, with the highest release of endotoxin per killed bacterium for cefuroxime, lower for tobramycin and the lowest for the combination of the two drugs (P < 0.001). With increasing doses, there was a significant reduction (P < 0.001) in the propensity to release endotoxin. When the bacterial killing rate was correlated to the propensity to release endotoxin in bacteria exposed to tobramycin or the combination of tobramycin and cefuroxime, a significant negative correlation was found (P < 0.01). This reduction in endotoxin release was not caused by an unspecific endotoxin binding of tobramycin. CONCLUSIONS: Addition of tobramycin reduced the cefuroxime-induced endotoxin release per killed bacterium to a level which was even lower than that of tobramycin alone in spite of an increased killing rate. Increasing concentrations of tobramycin led to reduction in endotoxin release, which may be of benefit when dosing aminoglycosides once daily.

Serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) are elevated in advanced stages of non-Hodgkin's lymphomas.

The serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) were measured in 116 patients with non-Hodgkin's lymphomas (NHL) tested previously for soluble intercellular adhesion molecule-1 (sICAM-1). In contrast to Hodgkin's disease and chronic lymphocytic leukaemia, the sVCAM-1 levels in NHL patients were not significantly different from the levels of healthy controls (n = 31). However, sVCAM-1 was elevated in advanced stage disease, i.e. stages III + IV. Elevated serum levels of sVCAM-1 were associated with significantly poorer disease-free (p = 0.024) and overall (p = 0.02) survival. sVCAM-1 correlated poorly with other known prognostic variables (LDH, sTK and beta 2m) and with sICAM-1. None of the tested markers added prognostic information for disease-free survival independently of Ann Arbor stage and B-symptoms. The expression of VCAM-1 and ICAM-1 in tumour biopsies from 15 patients representing 7 different histologies were examined and compared with the serum levels of the soluble adhesion molecules. No correlation was found between the adhesion molecule expression by vascular endothelium and the corresponding serum levels.

Cervical spine fractures in the elderly: factors influencing survival in 65 cases.

To evaluate whether a cervical spine fracture increases the death risk in elderly patients, and to define risk factors, we studied the survival of 65 patients (26 women) with a mean age of 77 (66-99) years. 8 of the patients were tetraparetic. In 35 patients, the upper cervical spine was fractured. 7 patients suffered from ankylosing spondylitis. Severe co-morbidity was present in 16. Survival status and the date of death were retrieved from the government official personal registry. The expected survival was calculated from data retrieved from the Swedish National Board of Health and Welfare. Variables having a possible relation with survival (i.e., a p-value < 0.10 when entered into a Kaplan-Meier survival analysis) were used in a Cox multiple regression survival analysis. 53 (24-105) months after injury, 25 of the 65 patients had died. The survival was significantly lower than the expected values. Severe co-morbidity (risk ratio: 5,6), neurological injury (6,4), high age (1,1), and ankylosing spondylitis (5,5) proved to be significant risk factors for death. Thus, a cervical spine fracture may lead to earlier death in a patient with a severe co-morbidity. A neurological complication constitutes a risk also for a previously healthy individual. Patients having ankylosing spondylitis (with increased death risk) run a higher than normal risk of sustaining a cervical spine fracture.

Serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) are elevated in advanced stages of non-Hodgkin's lymphomas.

The serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) were measured in 116 patients with non-Hodgkin's lymphomas (NHL) tested previously for soluble intercellular adhesion molecule-1 (sICAM-1). In contrast to Hodgkin's disease and chronic lymphocytic leukaemia, the sVCAM-1 levels in NHL patients were not significantly different from the levels of healthy controls (n=31). However, sVCAM-1 was elevated in advanced stage disease, i.e. stages III+IV. Elevated serum levels of sVCAM-1 were associated with significantly poorer disease-free (p = 0.024) and overall (p = 0.02) survival. sVCAM-1 correlated poorly with other known prognostic variables (LDH, sTK and beta2m) and with sICAM-1. None of the tested markers added prognostic information for disease-free survival independently of Ann Arbor stage and B-symptoms. The expression of VCAM-1 and ICAM-1 in tumour biopsies from 15 patients representing 7 different histologies were examined and compared with the serum levels of the soluble adhesion molecules. No correlation was found between the adhesion molecule expression by vascular endothelium and the corresponding serum levels.

How do GPs use clinical information in their judgements of heart failure? A clinical judgement analysis study.

OBJECTIVE: To study general practitioners' (GP) clinical diagnoses of heart failure. DESIGN: A Clinical Judgement Analysis study. SETTING: Primary health care. SUBJECTS: Twenty-seven GPs from nine health centres in Stockholm County. INTERVENTION: Forty-five case vignettes, based on actual patients from two health centres in Stockholm, were presented to each GP. For each case vignette, the GPs judged the probability of heart failure. MAIN OUTCOME MEASURES: The GPs' assessments of the probability of heart failure in the case vignettes. The GPs' utilization of clinical information in their judgement strategies, as measured by the regression coefficients in a multiple regression equation, with the probability assessments as dependent and the clinical criteria as independent variables. RESULTS: The variation between the GPs' assessments of the probability of heart failure was considerable. The judgemental strategies differed between the doctors, the most important variables for most of them being lung and heart X-rays and a history of myocardial infarction. CONCLUSIONS: With new treatment recommendations, it has become increasingly important to identify patients with heart failure. This study demonstrates large differences in GPs' diagnoses of heart failure. An important source of this variation is the differences in how they make use of clinical information.

What is the long term value of multiphasic health screening and the initial judgement of benefit?

The long term effects of multiphasic health screening (MHS) are rarely studied. In 1964 a random sample of 546 women and 544 men born 1899, 1904, 1909, 1914 or 1919 equally distributed on cohorts from the Swedish town Eskilstuna were invited to examination. For several reasons 167 persons (15%) did not participate in the study. In 1969 the whole sample was invited to a second MHS together with a control group that had not been exposed to MHS. Furthermore, 79 of those alive 1989 born 1899 or 1904 and examined 1964 and 1969 were reexamined. Over all survival rate 1989 for those examined 1964 was for males 18% and for females 35%. Screening instruments 1964 and 1969 were questionnaires, laboratory tests, antropometric measurements, ECG, measurement of blood pressure, chest radiography, peak expiratory flow (PEF), tonometry and fundoscopy of the eyes, audiometric screening, dental, gynecological and general clinical examination. Systolic hypertension for both sexes, low PEF and smoking, low cholesterol in women were negatively related to survival. Of 18 diabetics only one was alive at follow-up. No association was found between BMI and mortality for men, but some (1964 p < 0.01; 1969 p < 0.05) for women. Altogether 87 individuals were 1969 judged to have had some benefit of the MHS in 1964, 40 of them substantial. This was, however, not statistically significantly associated with improved survival. Of the reexamined survivors 86% reported to be generally satisfied with their life situation. The prognostic value of graded benefit was analysed in some detail. The survival to age 85 in the group allotted any benefit was somewhat less good (37%) than in the group with no benefit (44%). The difference did not reach statistical significance.

[Interim analyses--a scientific dilemma]. / Interimsanalyser--ett vetenskapligt dilemma.

Interim analyses are nowadays an important part of clinical trials. Unfortunately, there is no consensus about when and how to conduct these analyses. In the field of statistics different schools promote different statistical methods. Since the choice of method can have a major impact on the results it is essential to be well informed about the problems, associated with interim analyses. One such problem concerns communication between statisticians and physicians. Close collaboration is required to facilitate good clinical trials. This paper highlights some of the statistical difficulties and relates these to the problem of collaboration between statisticians and physicians.

Survival and daily physical activity in patients treated for advanced midgut carcinoid tumors.

BACKGROUND: Prospects for survival and quality of life ought to influence treatment strategies in patients with midgut carcinoids. METHODS: A total of 121 patients with midgut carcinoid received a combined medical and surgical treatment from 1980 to 1993. In all, 158 operations were undertaken for removal of mesentericointestinal lesions and occasional liver metastases or as repeat intervention for abdominal complications. Survival was analyzed together with estimates of daily physical activity during follow-up. RESULTS: Cause of death (63 patients) included carcinoid heart disease (41%) and cachexia (mesentericointestinal entrapment, 35%). Median survival was 11 years in patients with irresectable mesenteric metastases, 7 years with liver metastases, and 1 year with extraabdominal spread. Extensive liver metastases or substantial weight loss (9 kg or greater) reduced survival to a median of 4 to 5.5 years, and surgically treated intestinal ischemia reduced survival to a median of 8 years. Patients with carcinoid syndrome survived a median 7 years, those with 5-hydroxyindoleacetic acid values greater than 500 mumol/24 hr or a valvular heart disease survived a median of 5 years, those with heart failure a median of 2.5 years. Most patients retained an acceptable daily physical activity; impairment occurred in cases of malnutrition, high 5-hydroxyindoleacetic acid values, or heart valve fibrosis, and activity was markedly reduced in the presence of extraabdominal metastases or overt heart disease. CONCLUSIONS: Favorable survival statistics and the maintenance of daily physical activity support active medical and surgical management in patients with advanced midgut carcinoids.

Evaluation of platelet function using the in vitro bleeding time and corrected count increment of transfused platelets. Comparison between platelet concentrates derived from pooled buffy coates and apheresis.

The functional capacity of transfused platelets was evaluated with in vitro bleeding time (IVBT) and corrected count increment (CCI) in order to compare platelet concentrates (PCs) derived from pooled buffy coats (BC-PCs) with PCs collected by apheresis (A-PCs). The suspension medium in the BC-PCs was 30% CPD plasma and 70% of an additive solution (containing sodium and potassium chloride, sodium citrate and phosphate, mannitol), and in the A-PCs the medium was 100% CPD plasma. IVBT was evaluated using a Thrombostat 4000/2. BC-PC and A-PC were transfused 57 and 41 times, respectively to 36 patients with chemotherapy-induced thrombocytopenia. PCs transfused within 2 days of donation were considered fresh, and those transfused within 3-5 days were considered stored. IVBT was determined before, as well as 10-30 min and 24 h after transfusion; CCI was determined 10-30 min and 24 h after transfusion. The median pretransfusion IVBT value was 486 s. It was measurable in 21 of 98 (21%) of the transfusions, i.e. below the cutoff limit of 486 s. Ten to 30 min after transfusion, the IVBT showed a measurable reduction in 90% of the transfusions with fresh BC-PCs, 92% of those with fresh a-PCs, 63% of those with stored BC-PCs and 79% of those with stored A-PCs. After 24 h, the corresponding values were 63% for fresh BC-PCs, 50% for fresh A-PCs, 26% for stored BC-PCs and 38% for stored A-PCs. The median value of CCI 10-30 min after transfusion was 20 for fresh BC-PCs, 17 for fresh A-PCs, 16 for stored BC-PCs and 14 for stored A-PCs. The difference in IVBT between fresh and stored BC-PCs was significant (p = 0.032), unlike that between fresh and stored A-PC. After 24 h the corresponding values were 7 for fresh BC-PCs, 4 for fresh A-PCs, 4 for stored BC-PCs and 3 for stored A-PCs. When all transfusions with fresh PCs (BC-PCs + A-PCs) were compared with all transfusions with stored PCs, a statistical difference was demonstrated in both CCI (p = 0.027) and IVBT (p = 0.043). Spearman's rank correlation coefficient (rs) was -0.41 between CCI and IVBT < 486 s 10-30 min after transfusion, and -0.55 between the posttransfusion platelet count and IVBT, indicating a relatively poor correlation between CCI and IVBT, and a slightly better correlation between platelet count and IVBT. In conclusion, BC-PCs showed a slightly higher CCI and a better response in IVBT than A-PCs. No statistical difference was demonstrated between BC-PCs and A-PCs transfused within 2 days after donation, with respect to function and recovery in vivo. BC-PCs stored for 3 days or more showed about the same CCI and IVBT as stored A-PC but significantly lower CCI and higher IVBT than fresh BC-PCs. This may indicate that the preparation and/or storage conditions were not optimal. IVBT seems to be a useful possibility to test the in vivo behavior of transfused platelets.

Outcome after limited posterior surgery for thoracic and lumbar spine metastases.

The efficacy of 'limited posterior surgery' for metastases in the thoracic and lumbar spine was studied prospectively in 51 patients (32 men and 19 women, mean age 64 years). The most common primary tumors were prostate, breast, and renal carcinoma, 37 patients had metastases in the thoracic spine and 14 in the lumbar spine. Indications for surgery were severe pain or neurologic deficit. Of the 46 patients with neurologic symptoms, 25 were unable to walk. Surgery was confined to direct or indirect decompression and stabilization with a pedicle screw fixator over few segments as possible. Pain, as well as a variety of functional performance parameters and residential status were registered preoperatively and after surgery at 3, 6, 9, and 12 months, and at 6-monthly intervals thereafter. Pain was rated by the patient on a Visual Analog Scale, and functional performance was assessed with the Eastern Co-operative Oncology Group (ECOG) Performance Status Scale. We had no perioperative neurologic deterioration or death. Nineteen of the 25 nonambulatory patients regained their walking ability. Postoperative pain relief was significant and lasting over time. Nearly half of the patients attained improvement in functional performance. The median survival was 8 months. Older age and intact postoperative walking ability were positive factors for survival.