Baseline characteristics, disease severity and treatment history of patients with atopic dermatitis included in the German AD Registry TREATgermany.

BACKGROUND: The Atopic Dermatitis (AD) TREATgermany registry was initiated by the German Society for Dermatology (DDG) in 2011 to evaluate the 'real-life' situation of health care for patients with AD. OBJECTIVES: Interim data analysis on baseline characteristics as well as current and prescribed systemic treatments of the TREATgermany registry patients. METHODS: Patients (≥18 years) with moderate-to-severe AD [objective (o)SCORAD > 20], or with current or previous anti-inflammatory systemic treatment for AD within 24 months, were included and are followed up over at least 24 months. To assess clinical signs, the eczema area severity index (EASI, 0-72), the oSCORAD (0-83) and the Investigator Global Assessment (IGA; 6-point scale) were used. The disease severity was globally scored by the patients [Patient Global Assessment (PGA); six-step Likert scale]. Disease symptoms were assessed by the patient-oriented eczema measure (POEM, 0-28) and numeric rating scales (NRS, 0-10). Health-related quality of life was measured using the dermatological life quality index (DLQI, 0-30). RESULTS: A total of 612 patients were recruited across 32 sites between 06/2016 and 01/2019 (mean age: 42.6 ± 14.2 years; mean oSCORAD: 40.8 ± 16.3). The mean POEM score was 16.3 ± 7.5. Pruritus was rated highest among subjective symptoms (NRS: 5.4 ± 2.7). The mean DLQI value was 11.3 ± 7.5. The frequency of arterial hypertension was lower (20.8%) compared with the general population, whilst this was higher for depression (10%). More than 60% of the patients had received systemic glucocorticosteroids, and 36.8% had received cyclosporine A prior to inclusion. Dupilumab was the leading substance documented as either 'current' (12.1%) or 'prescribed' (31.4%) at baseline. CONCLUSIONS: These 'real-life' data clearly demonstrate the substantial disease burden. Most of TREATgermany patients were already treated with or prescribed dupilumab at baseline. Moreover, current findings indicate the urgent need for further alternative agents in order to achieve a perceptible improvement of quality of life of patients with moderate-to-severe AD.

Economic burden of diagnosed pertussis among individuals with asthma or chronic obstructive pulmonary disease in the USA: an analysis of administrative claims.

Individuals with chronic respiratory conditions may be at increased risk for pertussis. We conducted a retrospective administrative claims analysis to examine the incidence and economic burden of diagnosed pertussis among adolescents and adults in the USA with chronic obstructive pulmonary disease (COPD) or asthma. Patients aged ⩾11 years with diagnosed pertussis and pre-existing COPD (n = 343) or asthma (n = 1041) were matched 1:1 to patients with diagnosed pertussis but without COPD or asthma. Differences in all-cause costs ('excess' costs) during the 45-day and 3-month and 6-month periods before and after the pertussis index date were calculated; adjusted excess costs were estimated via multivariate regressions. The incidence of diagnosed pertussis was higher among patients with COPD or asthma than among matched patients. Compared with matched patients, patients with pertussis and pre-existing COPD or asthma accrued greater all-cause adjusted costs across study periods ($3694 and $1193 more, respectively, in the 45-day period; $4173 and $1301 more in the 3-month period; and $6154 and $1639 more in the 6-month period; all P < 0·0001). Patients with pre-existing COPD or asthma experience an increased economic burden after diagnosed pertussis and may especially benefit from targeted tetanus, diphtheria, and acellular pertussis vaccination strategies.

Prevalence and factors associated with overweight and obesity in dogs presenting to French university veterinary teaching hospitals during the COVID-19 pandemic.

Pet obesity is still a major health issue, which is considered an epidemic by some researchers. Prevention is one of the cornerstones of veterinary care, emphasizing the importance of proactive measures. Human lifestyle was affected during the COVID-19 pandemic, resulting in an increased overweight prevalence in the population. The prevalence of overweight and obesity in dogs during this period has been poorly explored. This study's objectives were to assess the percentage of the French dog population with overweight and obesity, compare the results with a study conducted before the COVID-19 pandemic, and investigate any potential changes in the risk factors. The study collected data through a survey completed by dog owners during their pets' vaccination visits at university veterinary hospitals of Maisons-Alfort (Paris) and Toulouse, in France, between 2020 and 2022. The veterinarian recorded the dog's weight and the body condition score using a 9-point scale. The study included a total of 309 dogs. Of these, 1.6 % were underweight, 63.1 % had an ideal body condition, and 35.3 % were overweight, including 2.3 % of all dogs classified as obese. During the pandemic, French dog diets shifted towards increased commercial food consumption and twice-daily feedings compared to a 2003 study. Factors positively associated with overweight were being female (OR = 3.55; 95 % CI: 1.65-8.01; P=0.002), being senior (OR=4.91; 95 % CI: 2.07-12.2; P<0.001) or geriatric (OR=5.81; 95 % CI: 2.04-17.0; P=0.001) and having an owner underestimating dog's body condition (OR=74.1; 95 % CI: 29.8-215; P<0.001). Recognizing the impact of owner perception enables early intervention strategies, such as educating owners during consultations and conducting teaching sessions at the clinic. This proactive approach could contribute to improved health outcomes and help prevent the onset of obesity-related issues in dogs. The new trends in dogs' diets may have global relevance due to the pandemic's widespread impact. Although no immediate impact on overweight is evident, ongoing research is crucial to understand the pandemic's long-term effects.

Delayed suprachoroidal hemorrhage after Descemet Stripping Automated Endothelial Keratoplasty (DSAEK).

This study, a case series of 2 patients and a literature review, aims to describe the second and third known cases of delayed suprachoroidal hemorrhage after Descemet stripping automated endothelial keratoplasty. The suprachoroidal hemorrhage is defined as the presence of blood in the suprachoroidal space; final visual acuity is rarely greater than 0.1 (decimal scale). Both cases presented had known risk factors: high myopia, previous ocular surgeries, arterial hypertension, and being under anticoagulant therapy. The diagnosis of delayed suprachoroidal hemorrhage was made at the 24-h follow-up visit, as they recalled a sudden and tremendous acute pain hours after surgery. Both cases were drained through a scleral approach. Delayed suprachoroidal hemorrhage is a rare but devastating consequence that can occur after Descemet stripping automated endothelial keratoplasty. Awareness of the most critical risk factors allows for early identification, which is of paramount importance for the prognosis of these patients.

Effects of Mental Health Paraprofessional Training for Filipina Foreign Domestic Workers in Singapore.

Research has found that 24% of foreign domestic workers (FDWs) in Singapore have poor mental health (24%), with depressive symptoms being identified as the second most severe psychological symptoms [1]. The study assessed the acceptability and effectiveness of a 4-week cognitive behavioral therapy (CBT)-based paraprofessional training program for FDWs in Singapore on depression literacy and CBT knowledge (primary outcomes), depression-related stigma, as well as attitudes towards seeking professional help (secondary outcomes) immediately and 2 months following the training. Forty female Filipino FDWs were recruited and randomized into either a CBT-based paraprofessional training program or wait-list (WL) group. Participants completed outcome measures before, after, and 2 months following their training. No significant difference was found on changes on any of the outcome variables in the intervention group as compared to the WL group. Following training, both groups showed significantly improved depression literacy, CBT knowledge, and attitudes towards seeking professional help. These changes were sustained at 2-month follow-up. All participants indicated a high level of satisfaction with the training program. While findings from between-group analyses do not support the efficacy of the CBT-based paraprofessional training program in improving depression literacy and related outcomes, participation in the program was associated with improvements in several outcomes within the training group. Future research should explore adaptations to the program (e.g., in terms of training duration and modes of delivery) that would increase its efficacy in improving depression literacy and CBT knowledge among FDWs.

Cost-effectiveness of an Adjuvanted Recombinant Zoster Vaccine in older adults in the United States.

In the United States, herpes zoster (HZ) and related complications are estimated to result in approximately $1.3 billion in medical care costs and $1.7 billion in indirect costs annually. In this study, we compared the cost-effectiveness of a new Adjuvanted Recombinant Zoster Vaccine (RZV), containing recombinant varicella-zoster virus glycoprotein E and the AS01B Adjuvant System, versus No Vaccine, as well as versus the live attenuated HZ vaccine (Zoster Vaccine Live (ZVL)) in subjects aged 60+ years of age (YOA) and other age cohorts aged 50+ YOA. A multi-cohort Markov model was developed which follows 1 million individuals over their remaining lifetimes from the year of vaccination with annual cycle lengths. Second dose compliance for RZV was assumed to be 69%. Efficacy and waning parameters were derived from clinical trials for both vaccines. Epidemiological parameters, costs and utility model inputs were derived from US-specific population-based data. Costs and outcomes were discounted at 3% per year. Deterministic and probabilistic sensitivity analysis, along with scenario and threshold analysis were carried out to explore the overall uncertainty in the model. The model estimated that, compared to No Vaccine against HZ, RZV would prevent 103,603 HZ cases, 11,197 postherpetic neuralgia (PHN) cases, and 14,455 other complications, at an incremental cost of $11,863 per quality-adjusted life-year saved from a societal perspective. Compared to ZVL, the model estimated that, RZV would prevent 71,638 additional HZ cases, 6403 PHN cases, and over 10,582 other complications, resulting in net total societal cost savings of over $96 million. The results were robust to a wide range of sensitivity analyses. Vaccination against HZ with RZV is cost-effective compared to No Vaccine and cost-saving compared to ZVL, in the US population aged 60+ YOA. Clinicaltrial.gov. registered#: NA.

Travel-related Zika virus cases in Canada: October 2015-June 2017.

BACKGROUND: Zika virus (ZIKV) is an emerging mosquito-borne disease that can cause severe birth defects if contracted congenitally. Since late 2015, there has been a large increase in the number of travel-related cases of Zika virus infection in Canada. OBJECTIVE: The objective of this study was to describe the epidemiology of travel-related Zika cases in Canada from October 2015 to June 2017 and review them in the context of the international outbreak in the Americas. METHODS: Zika virus infections were confirmed by polymerase chain reaction (PCR) detection of viral RNA and/or the serological identification of ZIKV-specific antibodies in serum. Cases of ZIKV infection were identified by provincial and territorial health authorities, and reported on a regular basis to the Public Health Agency of Canada (PHAC). Case information requested included date of illness onset, age category, sex, pregnancy status, and location(s) and dates of travel. Estimates for the monthly number of Canadians travelling outside of Canada to other countries in the Americas were obtained from Statistics Canada and the International Air Transport Association (IATA). Data to produce the epidemic curves of autochthonous cases for each region of the Americas were extracted from country-specific epidemic curves on the Pan American Health Organization website. RESULTS: As of June 7, 2017, 513 laboratory confirmed cases and two Zika-related birth/fetal anomalies were reported across all 10 provinces. Illness in Canadian travellers generally coincided with outbreak intensity in the country of exposure rather than travel volume. There has been no evidence of autochthonous (local) transmission in Canada. Currently, cases are on the decline both in Canada and internationally. CONCLUSION: The surge in Canadian ZIKV infections in 2016 was directly related to the incursion and spread of ZIKV into the Americas. Although cases are now on the decline worldwide, it remains to be seen whether a resurgence of cases in previously affected or new areas will occur. Both outbreak intensity and seasonality of ZIKV transmission should be monitored over time in order to inform the timing of public health education campaigns, as some may turn out to be more effective in the off-peak travel season when the risk of disease transmission may be higher. Ongoing education and awareness among travellers, particularly for pregnant women and those planning pregnancies, is still indicated.

N-terminal-pro-brain natriuretic peptide, but not brain natriuretic peptide, is increased in patients with severe obesity.

Elevated body mass index (BMI) has been reported as a risk factor for heart failure. Prevention of heart failure through identification and management of risk factors and preclinical phases of the disease is a priority. Levels of natriuretic peptides as well as activity of their receptors have been found altered in obese persons with some conflicting results. We investigated cardiac involvement in severely obese patients by determining N-terminal-pro-brain natriuretic peptide (NT-proBNP) and brain natriuretic peptide (BNP) and attempting to correlate the levels of these peptides in serum and plasma, respectively, with BMI, duration of obesity, waist circumference, and echocardiographic parameters. Thirty-three patients with severe obesity (mean BMI: 46.39 kg/m(2), mean age: 39 years) were studied. The control group contained 30 healthy age-matched individuals (BMI: <25 kg/m(2), mean age: 43 years). The t-test and Spearman correlation were used for statistical analysis. Log-NT-proBNP was significantly higher (P = 0.003) in obese patients (mean 1.67, 95% CI: 1.50-1.83 log pg/mL) compared to controls (mean: 1.32, 95% CI: 1.17-1.47 log pg/mL). The Log-NT-proBNP concentration correlated with duration of obesity (r = 0.339, P < 0.004). No difference was detected in the Log-BNP concentration (P = 0.63) of obese patients (mean: 0.73, 95% CI: 0.46-1.00 log pg/mL) compared to controls (mean: 0.66, 95% CI: 0.51-0.81 log pg/mL). NT-proBNP, but not BNP, is increased in severely obese patients and its concentration in serum is correlated with duration of obesity. NT-proBNP may be useful as an early diagnostic tool for the detection of cardiac burden due to severe obesity.

The Canadian Rabies Management Plan: An integrated approach to the coordination of rabies activities in Canada.

Although human cases of rabies are exceptionally rare in Canada, rabies remains endemic in some animal populations thus creating the need for ongoing vigilance. Rabies has always been a shared responsibility among local, provincial/territorial and federal authorities, as reflected in the 2009 Canadian Rabies Management Plan. Since 2009, a number of changes in rabies management have occurred, including the development of new tests, an oral rabies vaccine for wildlife, lessons learned from recent animal cases and changes in federal, provincial and territorial responsibilities in 2014. Federal departments and agencies continue to support rabies management through a number of activities. As the rabies landscape continues to evolve, so too must the strategies and frameworks required to manage this disease. As a result, the Canadian Rabies Management Plan and the North American Rabies Management Plan are being revised.

Postcryopreservation growth of human CFU-GM: sequential examination of methodologic factors.

Postcryopreservation growth of human CFU-GM might provide insight into the reconstitutive potential of human marrow preparations cryopreserved for subsequent autologous hematopoietic reconstitution. Ultimately, the utility of such measurements will depend on: whether comparison of pre- and postcryopreservation CFU-GM values is a guide to loss of reconstitutive potency during or following cryopreservation, and whether such measurements are consistent and reproducible. In our hands, direct, unmanipulated plating of CFU-GM after freezing and thawing resulted in extremely poor CFU-GM growth. Consequently, we undertook a set of sequential experiments designed to optimize technical conditions for growing human CFU-GM after cryopreservation. Utilizing stepwise examinations of washing, multiple plating factors, dilution rate, and diluent, we were able to increase consistently fractional recovery of postcryopreservation CFU-GM growth per 2 X 10(5) cells plated from 8% to 56%. Our results underscore the importance that technical factors (other than freezing conditions) play in the postcryopreservation growth of human CFU-GM.

External Validation of a Referral Rule for Axial Spondyloarthritis in Primary Care Patients with Chronic Low Back Pain.

OBJECTIVES: To validate and optimize a referral rule to identify primary care patients with chronic low back pain (CLBP) suspected for axial spondyloarthritis (axSpA). DESIGN: Cross-sectional study with data from 19 Dutch primary care practices for development and 38 for validation. PARTICIPANTS: Primary care patients aged 18-45 years with CLBP existing more than three months and onset of back pain started before the age of 45 years. MAIN OUTCOME: The number of axSpA patients according to the ASAS criteria. METHODS: The referral rule (CaFaSpA referral rule) was developed using 364 CLBP patients from 19 primary care practices and contains four easy to use variables; inflammatory back pain, good response to nonsteriodal anti-inflammatory drugs, family history of spondyloarthritis and a back pain duration longer than five years. This referral rule is positive when at least two variables are present. Validation of the CaFaSpA rule was accomplished in 579 primary care CLBP patients from 38 practices from other areas. Performance of the referral rule was assessed by c-statistic and calibration plot. To fit the final referral rule the development and validation datasets were pooled leading to a total study population of 943 primary care participants. RESULTS: The referral rule was validated in 579 patients (41% male, mean age 36 (sd7.0). The percentage of identified axSpA patients was 16% (n=95). External validation resulted in satisfactory calibration and reasonable discriminative ability (c-statistics 0.70 [95% CI, 0.64-0.75]). In the pooled dataset sensitivity and specificity of the referral rule were 75% and 58%. CONCLUSIONS: The CaFaSpA referral rule for axSpA consists of four easy to use predictors for primary care physicians and has a good predictive value in this validation study. The referral rule has the potential to be a screening tool for primary care by identifying CLBP patients suspected for axSpA.

Q fever outbreak among travelers to Germany associated with live cell therapy - United States and Canada, 2014: a co-publication.

WHAT IS ALREADY KNOWN ON THIS TOPIC?: Q fever is a zoonotic disease caused by Coxiella burnetii and is usually transmitted through inhalation of air contaminated with animal excreta. The disease is considered to be underdiagnosed because symptoms are nonspecific and can vary from patient to patient, making diagnosis difficult. WHAT IS ADDED BY THIS REPORT?: During September-October 2014, the New York State Department of Health identified Q fever in five patients with exposure to a treatment known as live cell therapy, an alternative medicine practice involving injections of fetal sheep cells, which is a type of xenotransplantation. Investigation revealed that a group of U.S. residents traveled to Germany twice a year to receive this treatment. WHAT ARE THE IMPLICATIONS FOR PUBLIC HEALTH PRACTICE?: Clinicians should consider zoonotic diseases, such as Q fever, in patients whose history includes receipt of a treatment known as live cell therapy. International travel for xenotransplantation procedures can facilitate transmission of zoonotic disease.

[125I]iodo-epidermal growth factor binding and mitotic responsiveness of porcine granulosa cells are modulated by differentiation and follicle-stimulating hormone.

Epidermal growth factor (EGF) stimulates granulosa cell (GC) proliferation of certain species and modulates FSH-induced GC differentiation. The present study was undertaken to characterize the binding properties of the EGF receptor in porcine GCs to determine if the EGF responsiveness of mitotically active porcine GCs was related to their differentiated state and was regulated by reproductive hormones in vitro. Characterization of the EGF receptor-binding properties of porcine GCs revealed that saturation binding was achieved with 10 ng/ml [125I]iodo-EGF after 1 h at 37 C. In all states of differentiation, porcine GCs expressed few (less than 20,000/cell), specific, high affinity EGF receptors with apparent Kd values of 5.5 +/- 0.7 X 10(-10) M (mean +/- SEM; n = 6). Freshly harvested GCs obtained from small follicles were considered slightly differentiated (SDs) and bound, on the average, 2.6-fold more [125I]iodo-EGF than highly differentiated cells (HDs) obtained from large follicles which had further differentiated in vivo. The difference in binding was due to a decrease in receptor number and not to a change in receptor affinity. This relationship observed in freshly harvested cells was maintained in culture for a limited period. At 48 h of culture, the [125I]iodo-EGF-binding capacity of SDs was higher than that of HDs and was inversely related to the state of differentiation, as measured by [125I]iodo-LH/hCG-binding capacity. After 96 h, however, the EGF-binding capacity of HDs increased 3.7-fold from the level of binding at 48 h, while the LH/hCG-binding capacity decreased 10-fold. Conversely, the EGF-binding capacity of SDs decreased 28%, while the LH/hCG-binding capacity remained low. These experiments indicated that the state of GC differentiation was inversely correlated with EGF receptor number and that this relationship was not maintained in culture beyond 48 h. FSH treatment within the first 48 h of culture decreased the EGF-binding capacity of SDs 35% relative to the control value, but estradiol and dihydrotestosterone had no effect. FSH also regulated the mitotic responsiveness to EGF. EGF treatment of cultured SDs stimulated an 84% increase in cell number and a 178% increase in [3H]thymidine incorporation. These effects were suppressed by a high concentration of FSH. Thus, the ability of porcine GCs to bind EGF was changed with differentiation in vivo, while both EGF-binding capacity and mitotic responsiveness were regulated by exposure to FSH in vitro.

Epidermal growth factor enhances [125I]iodo-follicle-stimulating hormone binding by cultured porcine granulosa cells.

Epidermal growth factor (EGF) has been shown to have diverse effects on granulosa cells (GC). Although a potent mitogen for GC from several species, EGF attenuates many FSH-mediated processes associated with GC differentiation, suggesting that EGF promotes cell proliferation at the expense of cell differentiation. The extent to which EGF effects involve modulation of the FSH receptor level in proliferating GC has not been established. Accordingly, we investigated the effect of EGF on [125I]iodo-FSH binding by porcine GC isolated from small follicles maintained in monolayer cultures. Relative to cells cultured in medium with insulin alone, EGF treatment increased total monolayer [125I]iodo-FSH binding (per culture) 120% (P less than 0.005). This was due to a 40-50% (P less than 0.01) increase in binding per U protein and/or per U cell and a 40-60% (P less than 0.005) increase in both monolayer cell and protein contents. EGF stimulated GC hyperplasia, but not hypertrophy. Optimum EGF doses for increased total monolayer [125I]iodo-FSH binding and binding normalized per U protein or cell were 0.5 and 0.1 ng/ml, respectively. Fibroblast growth factor was 20- to 100-fold less potent than EGF, and thrombin was without effect. Whereas [125I]iodo-FSH binding per U protein or cell was not affected by the serum concentration of the culture medium, the EGF effects on total monolayer binding and cell proliferation were directly related to the serum concentration (P less than 0.005). Thus, EGF-mediated increases in total monolayer [125I]iodo-FSH binding were paralleled by increases in cell number. The equilibrium dissociation constants (Kd) for [125I]iodo-FSH binding to cells cultured with and without EGF were 5.3 and 2.5 X 10(-10) M, respectively. Thus, EGF treatment significantly increased FSH receptor number, but significantly decreased receptor-binding affinity (P less than 0.05). Chronic FSH treatment during monolayer culture decreased total monolayer [125I]iodo-FSH binding and binding per U protein or per cell and attenuated EGF-stimulated cell proliferation, but markedly stimulated cell hypertrophy. Thus, concomitant treatment with EGF and FSH stimulated cell hypertrophy rather than hyperplasia. EGF and FSH each would appear capable of modulating the action of the other with respect to GC function. Our results indicate that EGF-mediated GC proliferation is associated with the expression of FSH-binding sites. This appears to be due to both an increase in FSH receptors among the cell population and an increase in the monolayer cell population.(ABSTRACT TRUNCATED AT 400 WORDS)

Fatty acid composition of the human macula and peripheral retina.

The fatty acids in the human retina and the macular region were measured quantitatively (mole percent) by gas chromatography. The major fatty acids of the human retina and macula were palmitic, stearic, oleic, arachidonic, and docosahexaenoic. Surprisingly, there was much less docosahexaenoic acid in the macular region (15.9% of total) than in the peripheral retina (22.3% of total). There was a group of "other fatty acids," not any of the five major fatty acids, that were relatively more abundant in the macula (21.0% of total) than in the peripheral retina (10.7% of total). These results indicate that the human macula has a unique biochemical composition, which differs substantially from the peripheral retina. Establishment of the biochemical composition of the macula may be important for helping recognize possible changes associated with diseases such as age-related macular degeneration.

Spectrophotometric quantitation of rhodopsin in the human retina.

The rhodopsin content of the human retina was determined spectrophotometrically. Retinas were removed completely by using an in vitro technique based on a simulation of retinal detachment. This method provides a total recovery of rod outer segments which contain the rhodopsin visual pigment or its apoprotein, opsin. Using this improved dissection method followed by a crude preparation of the retina, an opsin-rhodopsin content of 6.20 +/- 0.64 nmol/retina (n = 9) was found. This is larger than values previously reported. Regeneration with a threefold excess of 11-cis-retinal improved the recovery of rhodopsin dramatically because the corneas of these human donor eyes were removed for corneal transplant surgery under relatively bright light that bleaches the retina nearly completely. The amount of rhodopsin that can be isolated will be sufficient for studies on early events in visual transduction using laser photolysis.

The use of biosynthetic human growth hormone to augment ovulation induction with buserelin acetate/human menopausal gonadotropin in women with a poor ovarian response.

The present study has demonstrated the usefulness of GH in augmenting buserelin acetate/hMG to stimulate the rate of growth of follicles in women regarded as poor responders. The PR achieved was extremely encouraging in a group of patients whose prognosis was otherwise poor. Further studies are required to confirm these preliminary data.

The optimum position of arthrodesis of the ankle. A gait study of the knee and ankle.

UNLABELLED: Findings from biomechanical analyses of gait were used to estimate the optimum position of arthrodesis of the ankle. Nineteen patients who were followed for an average of 10.4 years (range, four to seventeen years) were studied. By including the knee in the analysis as well as studying the effects on gait of different ground conditions, objective data for the weight-bearing extremities in the transverse, sagittal, and coronal planes were generated. Genu recurvatum was shown to be associated with a plantar-flexion position of fusion of the ankle. Laxity of the medial collateral ligament of the knee was noted in twelve patients (63 per cent). Among these patients, in three (16 per cent) the laxity was graded as moderate to severe, possibly due to external rotation of the extremity during gait to avoid rolling over the rigid plantar-flexed ankle. The patterns of gait showed that a valgus position of the arthrodesis is more advantageous and provides more normal gait, particularly on uneven ground. To attain more normal function of the knee and improve performance on rough ground, the optimum position of arthrodesis of the ankle appears to be neutral flexion, slight (zero to 5 degrees) valgus angulation, and approximately 5 to 10 degrees of external rotation. Posterior displacement of the talus under the tibia tends to produce a more normal pattern of gait and decreases the stress at the knee. CLINICAL RELEVANCE: This study has shown the ideal position of fusion of the ankle to be neutral flexion, slight (zero to 5 degrees) valgus angulation of the hind part of the foot, and 5 to 10 degrees of external rotation. This position allows the greatest compensatory motion at the foot and places the least strain on the knee.

Children conceived by in vitro fertilisation after fresh embryo transfer.

AIMS: To compare the outcome in in vitro fertilisation (IVF) children (after fresh embryo transfer) from multiple and singleton births with one another, and with normally conceived control children. METHODS: A cohort of 278 children (150 singletons, 100 twins, 24 triplets and four quadruplets), conceived by IVF after three fresh embryos had been transferred, born between October 1984 and December 1991, and 278 normally conceived control children (all singletons), were followed up for four years after birth. They were assessed for neonatal conditions, minor congenital anomalies, major congenital malformations, cerebral palsy and other disabilities. Control children, all born at term, were matched for age, sex and social class. RESULTS: The ratio of male:female births was 1.03. Forty six per cent of IVF children were from multiple births; 34.9% were from preterm deliveries; and 43.2% weighed less than 2500 g at birth. The IVF singletons were on average born one week earlier than the controls, weighed 400 g less, and had a threefold greater chance of being born by caesarean section. The higher percentage of preterm deliveries was largely due to multiple births and they contributed to neonatal conditions in 45.0% of all IVF children. The types of congenital abnormalities varied: 3.6% of IVF children and 2.5% of controls had minor congenital anomalies, and 2.5% of IVF children and none of the controls had major congenital malformations. The numbers of each specific type of congenital abnormality were small and were not significantly related to multiple births. IVF children (2.1%) and 0.4% of the controls had mild/moderate disabilities. They were all from multiple births, including two children with cerebral palsy who were triplets. CONCLUSIONS: The outcome of IVF treatment leading to multiple births is less satisfactory than that in singletons because of neonatal conditions associated with preterm delivery and disabilities in later childhood. A reduction of multiple pregnancies by limiting the transfer of embryos to two instead of three remains a high priority.