Contribution of medico-administrative databases to health vigilance: example of post-oocyte retrieval infections.

STUDY QUESTION: Can we monitor post-oocyte retrieval infections in the French national health data system to complement the French ART vigilance system? SUMMARY ANSWER: Medico-administrative databases provide a more comprehensive view of post-oocyte retrieval infections and can be used to detect abnormal increases in frequency and outlier ART centers as a complementary tool to the ART vigilance system. WHAT IS KNOWN ALREADY: The various studies of ART complications are reassuring, showing relatively low overall complication rates. Nonetheless, the European Union has set up a vigilance system to monitor these complications. However, this system is not an exhaustive source of information and does not provide a complete overview of post-ART complications. STUDY DESIGN, SIZE, DURATION: The study population was identified from the comprehensive French national hospital discharge database. It included women under 46 years of age undergoing an oocyte retrieval in 2019, classified into three population subgroups according to the indication of oocyte retrieval: infertility (IF) , fertility preservation (FP), and oocyte donation (OD) . The study population included 52 098 women who had undergone 65 948 oocyte retrievals in 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS: Hospital stays and delivery of antibiotics within 31 days after oocyte retrieval were analyzed. Women and infections were characterized according to various characteristics (age, comorbidities, indication of oocyte retrieval, type of hospital stay, length of hospital stay, type of antibiotherapy, etc.). Multivariate analysis was performed to determine the relation between the occurrence of infection and women's characteristics, and results are expressed as odds ratios (ORs) and 95% CI. A funnel plot and a box plot were used to compare the infection rate per center with the national average and to detect outliers. MAIN RESULTS AND THE ROLE OF CHANCE: Infections in the month following the oocyte retrieval represented 6.9% of the procedures in 2019 (n = 4522). Of these infections, 112 were hospitalized (0.2% of oocyte retrievals), and 4410 were non-hospitalized (6.7% of oocyte retrievals). The hospitalized infections were essentially gynecological infections (40.9%) and urinary tract infections (23.5%). In 87.9% of non-hospitalized infections, a single antibiotic therapy was prescribed. Mixed-effect model analysis showed that the risk of infection was significantly higher in women under 30 years of age, in the FP population, in supplementary universal health coverage (CMU-C) beneficiaries, and women with endometriosis. Funnel plot and box plot analysis showed that three ART centers have an infection rate significantly higher than the national average. In the three centers that stand out from all the others, the objective is to return to these centers to understand the possible reasons for this observed rate and to implement corrective measures. LIMITATIONS, REASONS FOR CAUTION: Despite all its advantages, the French national health data system presents some limitations, such as the risk of inappropriate coding. Another limitation of this study is that we cannot confirm an attributable relation between the infection and the ART procedure, even if the delay of 31 days after oocyte retrieval is consistent with the occurrence of a post-retrieval complication. In addition, antibiotics may be prescribed as a 'precautionary' measure in certain situations (women with a susceptibility to infection, complicated procedures), or as antibiotic prophylaxis for embryo transfer. WIDER IMPLICATIONS OF THE FINDINGS: Despite the limits in identifying post-ART infections in medico-administrative databases, this approach is a promising way to complement the ART vigilance reporting system. This concept developed for infections will also be generalized to other complications with regular feedback to professionals. STUDY FUNDING/COMPETING INTEREST(S): No specific funding was sought for the study. The study was supported by the Agence de la biomédecine, France. The authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Novel anticonvulsive effects of progesterone in a mouse model of hippocampal electrical kindling.

Progesterone is a known anticonvulsant, with its inhibitory effects generally attributed to its secondary metabolite, 5α,3α-tetrahydroprogesterone (THP), and THP's enhancement of GABAA receptor activity. Accumulating evidence, however, suggests that progesterone may have non-genomic actions independent of the GABAA receptor. In this study, we explored THP/GABAA-independent anticonvulsive actions of progesterone in a mouse model of hippocampal kindling and in mouse entorhinal slices in vitro. Specifically, we examined the effects of progesterone in kindled mice with or without pretreatments with finasteride, a 5α-reductase inhibitor known to block the metabolism of progesterone to THP. In addition, we examined the effects of progesterone on entorhinal epileptiform potentials in the presence of a GABAA receptor antagonist picrotoxin and finasteride. Adult male mice were kindled via a daily stimulation protocol. Electroencephalographic (EEG) discharges were recorded from the hippocampus or cortex to assess "focal" or "generalized" seizure activity. Kindled mice were treated with intra-peritoneal injections of progesterone (10, 35, 100 and 160mg/kg) with or without finasteride pretreatment (50 or 100mg/kg), THP (1, 3.5, 10 and 30mg/kg), midazolam (2mg/kg) and carbamazepine (50mg/kg). Entorhinal cortical slices were prepared from naïve young mice, and repetitive epileptiform potentials were induced by 4-aminopyridine (100µM), picrotoxin (100µM) and finasteride (1µM). Pretreatment with finasteride did not abolish the anticonvulsant effects of progesterone. In finasteride-pretreated mice, progesterone at 100 and 160mg/kg decreased cortical but not hippocampal afterdischarges (ADs). Carbamazepine mimicked the effects of progesterone with finasteride pretreatments in decreasing cortical discharges and motor seizures, whereas midazolam produced effects similar to progesterone alone or THP in decreasing hippocampal ADs and motor seizures. In brain slices, progesterone at 1µM inhibited entorhinal epileptiform potentials in the presence of picrotoxin and finasteride. We suggest that progesterone may have THP/GABAA-dependent and independent anticonvulsive actions in the hippocampal-kindled mouse model.

Information required to provide informed consent for endoscopy: an observational study of patients' expectations.

BACKGROUND AND STUDY AIMS: The aim of this study was to determine how much information patients require about the risk of complications in order to provide informed consent to undergo endoscopy. PATIENTS AND METHODS: Endoscopic complications and their consequences were discussed with consecutive patients who had undergone endoscopy. The patients were asked how common each complication would have to be for them to require information about the complication before providing adequately informed consent. RESULTS: Data were obtained from 150 gastroscopy patients (51% male, median age 55.5 years) and 150 colonoscopy patients (60% male, median age 54.4 years). Patients in both groups were more likely to want to know about major rather than minor complications at a lower level of risk (P < 0.001 at a risk greater than one in 1000). Similar proportions of gastroscopy patients (n = 29, 19%) and colonoscopy patients (n = 21, 14 %) wanted to know about all possible complications, no matter how inconsequential or rare. Colonoscopy patients were less likely to want no information about any complications than gastroscopy patients (n = 1, 0.7% and n = 15, 10%, respectively; P < 0.001). CONCLUSIONS: The information patients require in order to provide informed consent is very variable. Many appear to make a judgement about the need for information depending on the perceived severity of the complication, but some want information about all complications, irrespective of risk and severity. The level of risk at which they require this information is likely to be higher than the level used by doctors who are obtaining consent from patients. The process may be improved by providing procedure-specific information leaflets that offer information regarding common and serious complications.

Motion detection and correction using multi-rotation 180 degrees single-photon emission tomography for thallium myocardial imaging.

Patient and organ motion is a potentially limiting factor in gamma camera single-photon emission tomography (SPET) imaging, as highlighted in stress thallium myocardial SPET, where the heart may exhibit a systematic axial motion (cardiac creep) following stress. Multi-rotation SPET has previously been described as a means of obtaining better raw data for motion detection and correction. This study describes the validation of a computerised motion detection algorithm applied to multi-rotation SPET, and reports measured motions in thallium myocardial stress SPET studies from a single-headed gamma camera. Forty-two patients underwent pharmacological stress (dipyridamole) with leg raising, with injection of 75 MBq thallium-201 and imaging after a 10-min delay to detect or evaluate coronary artery disease. Multi-rotation gamma camera SPET was performed with a single-headed gamma camera, with five sequential rapid (4.5 min) continuous SPET mode rotations over 180 degrees. A one-dimensional cross-correlation alignment technique was applied to the projection images to perform motion detection and correction in the axial direction prior to combining the five data sets for tomographic reconstruction. Validation of the cross-correlation alignment analysis was carried out by performing imaging with measured whole-body axial motions in nine subjects, and by reproducibility measurements on multi-rotation data sets. The effect of the applied motion correction was evaluated by calculating mean differences between image pairs before and after shifting, and the general reliability of the automatic motion detection was checked to within one pixel by visual assessment of 160 image pairs. Validation measurements of the cross-correlation technique gave a mean absolute error of 1.5+/-0.4 mm (0.24+/-0.06pixels) with a maximum error of 3.7 mm (0.6 pixels). In 40 subjects undergoing pharmacological stress 201Tl myocardial SPET imaging, the mean cardiac axial creep movement was calculated as 3.1+/-0.7 mm (0. 49+/-0.11 pixels), with 13 out of 40 (32%) having a calculated motion of 1 pixel (6.3 mm) or more. The automatic image shift was visually judged to be within 1 pixel in all 160 image pair analyses, and the mean pixel value difference between image pairs was reduced following image shifting. It is concluded that multi-rotation 180 degrees SPET imaging provides raw data which allow objective and accurate motion detection of cardiac motion in thallium stress myocardial imaging, whilst the one-dimensional cross-correlation technique demonstrates adequate accuracy and reliability to be applied as an automatic motion screening technique on these data.

Dipyridamole stress thallium-201 perfusion abnormalities in patients with hypertrophic cardiomyopathy. Relationship to clinical presentation and outcome.

AIMS: Thallium-201 perfusion abnormalities are common in patients with hypertrophic cardiomyopathy and may be associated with an adverse prognosis in the young. The aim of this study was to prospectively determine the relationship between thallium-201 defects during dipyridamole stress to clinical presentation and outcome in a large consecutive series of patients with hypertrophic cardiomyopathy. METHODS/RESULTS: Thallium-201 single photon computed tomography was performed in 216 patients with hypertrophic cardiomyopathy during dipyridamole stress (0.5 mg. kg-1). Fixed perfusion defects occurred in 25%, and reversible defects in 22%. A combination of defects was present in 7%. Fixed defects were associated with: a history of syncope (17 of 46 with, vs 36 of 170 without syncope, P = 0.03); larger left ventricular end-diastolic (46.9 +/- 7.4 mm vs 43.3 +/- 6.4 mm; P = 0.001) and end-systolic dimension (30.2 +/- 8.4 mm vs 24.5 +/- 5.9 mm, P < 0.0001); increased left atrial diameter (46.1 +/- 8.1 mm vs 40.5 +/- 7.7 mm, P < 0.0001); lower fractional shortening (35.9 +/- 10.4% vs 43.8 +/- 8.6%, P < 0.0001): and lower maximal exercise oxygen consumption (24.2 +/- 8.1 ml. min-1. kg-1 vs 29.4 +/- 8.8 ml. min-1. kg-1, P < 0.0003). Reversible defects did not correlate with symptomatic status, but were associated with: larger left atrial dimensions (44.5 +/- 8.1 mm vs 41.0 +/- 8.0 mm; P = 0.009) and greater maximal left ventricular wall thickness (24.0 +/- 7.0 mm vs 20.6 +/- 7.0 mm, P = 0.003). The mean follow up time was 41 +/- 21 months, range 0.6-124. There was no association between any thallium-201 abnormality and disease related death in young or adult patients. CONCLUSION: The present study shows that fixed thallium-201 perfusion defects detected during dipyridamole stress in patients with hypertrophic cardiomyopathy are associated with syncope, larger left ventricular cavity dimensions and reduced exercise capacity. Although the event rate was relatively small, there was no evidence for an association between thallium-201 defects and survival.

Quantification of inflammatory bowel disease activity using technetium-99m HMPAO labelled leucocyte single photon emission computerised tomography (SPECT).

Technetium-99m HMPAO labelled white cell bowel uptake was quantified in 23 patients with suspected colitis by means of the novel technique of single photon emission computerised tomography (SPECT) using a standard gamma-camera. Uptake in colon segments was quantified on transaxial images and expressed as a fraction of marrow uptake (SPECT score). Segmental histological disease activity was assessed at colonoscopy (20) or at surgery (3). Segmental histology score correlated with SPECT score r = 0.79 (p < 0.001). Overall SPECT score for all affected segments correlated with Crohn's disease activity index (CDAI) r = 0.66, p = 0.001 and with laboratory activity indices; erythrocyte sedimentation rate r = 0.44, p = 0.03, C reactive protein r = 0.38, p = 0.05, and albumin r = -0.46, p = 0.03. Small bowel SPECT score in 13 patients correlated with CDAI r = 0.65, p < 0.01 but not with erythrocyte sedimentation rate or C reactive protein. Five patients with positive small bowel white cell uptake had normal C reactive protein and erythrocyte sedimentation rate. Overall SPECT score for disease at all sites correlated with both CDAI and with laboratory indices of inflammation. 99mTc HMPAO SPECT provides non-invasive and accurate quantification of inflammatory bowel disease activity in both large and small bowel and may be useful in the objective evaluation of treatment for inflammatory bowel disease.

Regional thallium-201 washout and myocardial hypertrophy in hypertrophic cardiomyopathy and its relation to exertional chest pain.

The mechanism of exertional chest pain in hypertrophic cardiomyopathy is uncertain, but may relate to myocardial ischemia. To study the mechanism of exertional chest pain in hypertrophic cardiomyopathy, dipyridamole-stress thallium-201 single-photon emission computed tomography was performed in 82 consecutive patients, and the 3-hour washout of thallium in relation to the tomographic image, regional wall thickness on echocardiography, and other clinical findings was analyzed. There was a weak inverse correlation of regional washout and wall thickness in 298 analyzed quadrant areas (r = -0.29; p = 0.0001). Twenty-five patients (31%) had history of exertional chest pain, and showed a significantly lower total washout and greater maximal left ventricular wall thickness than did those without chest pain (32 +/- 10% vs 37 +/- 9% [p = 0.03], and 27 +/- 7 vs 23 +/- 7 mm [p = 0.03], respectively). Even in mildly and nonhypertrophied areas, patients with chest pain had a significantly lower regional washout than did those without pain (33 +/- 10% vs 38 +/- 9%; p = 0.02), despite similar left ventricular wall thickness (12 +/- 2 vs 11 +/- 3 mm; p = NS). Reduced washout was strongly associated with exertional chest pain and was observed in myocardial regions that had normal as well as increased thickness, which indicates that this abnormality of thallium kinetics is a function of the disease process and not the magnitude of left ventricular hypertrophy.

Abnormal lymph drainage in patients with chronic venous leg ulcers.

BACKGROUND: Edema often occurs in association with venous leg ulcers. OBJECTIVE: Our purpose was to assess lymphatic function in the legs of patients with venous leg ulcers. METHODS: Quantitative lymphoscintigraphy was performed in 22 normal control subjects, 32 patients with venous leg ulcers, and 7 patients with varicose veins only. RESULTS: Lymph drainage declined with age in the normal controls (r = -0.57; p = 0.0001). Lymphatic function was reduced in the ulcerated legs compared with normal limbs (age < 65 years; p < 0.0001) and in edematous legs compared with nonedematous legs (age > 65 years; ulcerated legs, p = 0.016; nonulcerated legs, p = 0.021). Lymph drainage was lower in the legs of patients with varicose veins only (p = 0.004). CONCLUSION: Impaired lymphatic function is associated with both venous leg ulcers and chronic venous hypertension.

Asymmetry of cardiac [123I] meta-iodobenzyl-guanidine scans in patients with ventricular tachycardia and a "clinically normal" heart.

OBJECTIVE: Patients with exercise induced ventricular tachycardia associated with a "clinically normal" heart may have an abnormality of the regional distribution of the cardiac sympathetic nerve supply. In this study the regional distribution of the myocardial nerve supply in patients with ventricular tachycardia (VT) and control subjects was examined by [123] meta-iodobenzylguanidine (MIBG) scanning. PATIENTS AND DESIGN: Eight patients with exercise induced VT and seven patients with VT unrelated to exercise with "clinically normal" hearts were studied and compared with a control group of six subjects with atrioventricular reentrant tachycardia not related to exercise and eight patients with angiographically normal left ventricular function and normal coronary anatomy who had thallium scans without evidence of ischaemia or fixed perfusion deficits. METHODS: Single photon emission computed tomography gamma scanning was performed in patients three hours after intravenous injection of MIBG. The left ventricular MIBG uptake data was processed into bull's-eye target plots. The inferior portion of the scan frequently showed artefact due to uptake of MIBG in the liver or spleen and was not used for statistical analysis. Asymmetry of uptake was defined as a ratio of uptake exceeding 1.25 in the upper quadrants (posterior (anterolateral free wall)/anterior (anteroseptal region)) of the MIBG scan. RESULTS: Patients with VT had a higher proportion of asymmetrical MIBG scans (47%) than subjects in the control groups (0%) and this was particularly obvious in the patients with exercise induced VT (62.5%). This suggests that patients with VT may have relative denervation in the septal portion of the left ventricle leading to an imbalance of the sympathetic supply to the myocardium and locally imbalanced sympathetic or parasympathetic interactions. Considerable evidence from animal experiments suggests that imbalance of the sympathetic supply to the myocardium is important in the genesis of ventricular arrhythmia. CONCLUSIONS: These results support the hypothesis that selective denervation of the human myocardium may be an important mechanism in the genesis of VT in "clinically normal" hearts.

Investigation of the swollen limb with isotope lymphography.

The usefulness of isotope lymphography was evaluated in patients with chronic lower leg swelling. Forty patients (15 male, 25 female, age range 5 months-67 years) were assigned one of six clinical diagnoses based on clinical assessments, venography and lymphography. All the patients and seven normal controls were examined with bilateral isotope lymphography involving subcutaneous injection of 0.15 ml 99mTc-antimony sulphide colloid into the first web space of each foot. The percentage uptake of isotope-colloid in the inguinal lymph nodes at 1 and 2 h was equated with lymphatic function. Highly significant (P = 0.0001) differences existed between the different clinical groups and isotope lymphography discriminated well between oedema of lymphatic and non-lymphatic origin. Isotope lymphography appears to be a safe and useful test of lymphatic function.

Fecal leukocytosis, indium-111-labelled autologous polymorphonuclear leukocyte abdominal scanning, and quantitative fecal indium-111 excretion in acute gastroenteritis and enteropathogen carriage.

Abdominal scintiscans were performed and three-day fecal indium-111 radioactivity measured, following injection of indium-111-labeled polymorphonuclear leukocytes, in patients with acute gastroenteritis, enteropathogen carriage, exacerbations of chronic inflammatory bowel disease, and patients without gastrointestinal symptoms. The colon was more commonly inflamed than the small intestine in acute gastroenteritis. Fecal indium-111 radioactivity excretion was elevated in gastroenteritis and in chronic inflammatory bowel disease. The magnitude of the intestinal inflammatory response, as measured by fecal indium-111 excretion, is equivalent in acute gastroenteritis caused by a defined enteropathogen and exacerbations of chronic inflammatory bowel disease. All patients with microscopically detected fecal leukocytosis gave positive intestinal scintiscans, whereas negative scans were obtained on patients without fecal leukocytosis. The results of this study suggest that indium-111-labeled polymorphonuclear leukocytes can be used to study pathophysiology of the enteric inflammatory response in acute infectious gastroenteritis.