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Objective:To explore population characteristics, organization of health services and comparability of available information for very low birth weight or very preterm neonates born before 32 weeks’ gestation in 11 high-income countries contributing data to the International Network for Evaluating Outcomes of Neonates (iNeo).Study Design:We obtained population characteristics from public domain sources, conducted a survey of organization of maternal and neonatal health services and evaluated the comparability of data contributed to the iNeo collaboration from Australia, Canada, Finland, Israel, Italy, Japan, New Zealand, Spain, Sweden, Switzerland and UK.Results:All countries have nationally funded maternal/neonatal health care with >90% of women receiving prenatal care. Preterm birth rate, maternal age, and neonatal and infant mortality rates were relatively similar across countries. Most (50 to >95%) between-hospital transports of neonates born at non-tertiary units were conducted by designated transport teams; 72% (8/11 countries) had designated transfer and 63% (7/11 countries) mandate the presence of a physician. The capacity of ‘step-down’ units varied between countries, with capacity for respiratory care available in <10% to >75% of units. Heterogeneity in data collection processes for benchmarking and quality improvement activities were identified.Conclusions:Comparability of healthcare outcomes for very preterm low birth weight neonates between countries requires an evaluation of differences in population coverage, healthcare services and meta-data.

Levosimendan is a new calcium sensitizer developed for the treatment of congestive heart failure. Experimental studies indicate that levosimendan increases myocardial contractility and dilates both the peripheral and coronary vessels. Its positive inotropic effect is based on calcium-dependent binding of the drug to cardiac troponin C. It also acts as an opener of ATP-dependent potassium channels in vascular smooth muscle, thus inducing vasodilation. Although levosimendan acts preferentially as a calcium sensitizer it has also demonstrated selective phosphodiesterase III inhibitory effects in vitro. However, this selective inhibition does not seem to contribute to the positive action at pharmacologically relevant concentrations. Levosimendan has an active metabolite, OR-1896. Similarly to levosimendan, the metabolite exerts its positive inotropic and vasodilatory effects on myocardium and vasculature. The elimination half-life of levosimendan is about 1 hour. Thus, with intravenous administration, the parent drug rapidly disappears from the circulation after the infusion is stopped. The active metabolite, however, has a half-life of approximately 80 hours, and can be detected in circulation up to 2 weeks after stopping a 24-hour infusion of levosimendan. The intravenous formulation of levosimendan has been studied in several randomized comparative studies in patients with decompensated heart failure. Both patients with ischemic and non-ischemic etiology have participated in the studies. Levosimendan produces significant, dose-dependent increases in cardiac output, stroke volume and heart rate, and decreases in PCWP, mean blood pressure, mean pulmonary artery pressure, mean right atrial pressure and total peripheral resistance. With a loading dose, the effects on PCWP and cardiac ouput are seen within few minutes. There is no sign of development of tolerance even with a prolonged infusion up to 48 hours. Cardiac performance is improved with no significant increases in oxygen consumption or potentially malignant rhythm disorders. Due to the formation of an active metabolite, the hemodynamic effects are maintained up to several days after stopping levosimendan infusion. Compared to dobutamine, levosimendan produces similar increase in cardiac output but profoundly greater decrease in pulmonary capillary wedge pressure. On the contrary to dobutamine, the hemodynamic effects are not attenuated with concomitant beta-blocker use. Levosimendan has been shown to have favourable effects on symptoms of heart failure superior to placebo and at least comparable to dobutamine. Mortality and morbidity in levosimendan treated patients has been shown to be significantly lower when compared to dobutamine or placebo treated patients. The most common adverse events associated with levosimendan treatment are headache and hypotension, as a likely consequence of the vasodilating properties of the compound. In conclusion, levosimendan offers a new effective option for the treatment of acutely decompensated heart failure. Unlike traditional inotropes, levosimendan seems also to be safe in terms of morbidity and mortality.

To study what determines the arthritogenicity of bacterial cell walls, cell wall-induced arthritis in the rat was applied, using four strains of Lactobacillus. Three of the strains used proved to induce chronic arthritis in the rat; all were Lactobacillus casei. The cell wall of Lactobacillus fermentum did not induce chronic arthritis. All arthritogenic bacterial cell walls had the same peptidoglycan structure, whereas that of L. fermentum was different. Likewise, all arthritogenic cell walls were resistant to lysozyme degradation, whereas the L. fermentum cell wall was lysozyme sensitive. Muramic acid was observed in the liver, spleen, and lymph nodes in considerably larger amounts after injection of an arthritogenic L. casei cell wall than following injection of a nonarthritogenic L. fermentum cell wall. The L. casei cell wall also persisted in the tissues longer than the L. fermentum cell wall. The present results, taken together with those published previously, underline the possibility that the chemical structure of peptidoglycan is important in determining the arthritogenicity of the bacterial cell wall.

In the present trial, 101 patients with a clinical diagnosis of dandruff or seborrhoeic dermatitis with desquamation (dandruff) were treated with ketoconazole shampoo or hydrocortisone liniment in a double-blind (doubledummy) fashion. Significant reductions from baseline symptom severity (P<0.05) were seen in both treatment groups for desquamation, pruritis and erythema. There were no significant differences between the treatment groups at the endpoint. The proportion of patients who responded to the treatment, i.e. who were rated as normalized or markedly improved, was slightly higher in the ketoconazole group as judged by both investigator assessment (88% in ketoconazole vs. 80% in hydrocortisone group) and patient assessment (86% in ketoconazole vs. 82% in hydrocortisone group). Similarly, the percentage of normalized patients was higher in the ketoconazole group compared with the hydrocortisone group. The difference reached a statistically significant level (P = 0.011) in patient assessment. Seven of the 51 (13.7%) ketoconazole patients reported adverse events compared with 6 of the 50 (12%) hydrocortisone patients. All but one of the adverse events were dermatological or cosmetic in nature. It is obvious that the double-dummy design caused additional adverse events for ketoconazole patients, since the placebo liniment contained propylene glycol and isopropyl alcohol, which are known to cause skin irritation. Two ketoconazole patients discontinued the treatment due to irritation. Two hydrocortisone patients discontinued only the liniment treatment, one due to irritation and one due to itching. In conclusion, ketoconazole 2% shampoo is at least as effective as hydrocortisone 1% liniment in the treatment of dandruff. Ketoconazole shampoo may normalize the dandruff condition more often than hydrocortisone liniment does. Both treatments were well tolerated.

Antifungal drugs have been reported to have efficacy in the treatment of seborrhoeic disorders. This phenomenon has been attributed to their effects against Pityrosporum ovale which is often present on the diseased skin. In the present double-blind study, 74 patients with seborrhoeic dermatitis of the scalp with typ-ical symptoms such as scaling, erythema and itching, were randomly allocated to 4-weeks' treatment with clotrimazole - hydrocortisone liniment, hydrocortisone or plain propylene glycol-containing liniment base. In addition to symptoms, the presence of P. ovale was determined before and after treatment. All main symptoms were markedly relieved in all treatment groups. The area affected was clearly reduced in most patients after weeks' treatment. There were no statistically significant differences between treatments in any parameter evaluated. In the final global assessment, the number of patients with a good response was highest in the clotrimazole-hydrocortisone treatment group: 84% vs. 77% in the hydrocortisone group. However, the number of cured patients was the same (76%) in the liniment base group. The area of affected skin decreased during the treatment in most patients: 60% of all patients had at the most 5% of the initial area left. Data from the culture of P. ovule was evaluable from 54 patients. In only 14 cases, of which 5 were in the clotrimazole - hydrocortisone group, did the culture become negative after treatment. Eight patients discontinued the treatment prematurely; four due to lack of efficacy (three in the clotrimazole-hydrocortisone and one in the hydrocortisone group), one because of severe itching of the scalp (liniment base group) and three for other reasons. In conclusion, treatment of seborrhoeic dermatitis with plain hydrocortisone was as effective as the combination of clotrimazole and hydrocortisone. However, propylene glycol-containing liniment base was about as effective as the liniment with active drugs. The clinical results did not correlate well with P. ovule cultures.

The size of the gallbladder and the common bile duct as well as the contractility of the gallbladder were measured in infants under the age of 1 year. A total of 43 healthy infants were studied at their routine visit to the well-baby clinic at the ages of 6 weeks, 4 months, 8 months or 12 months. Gallbladder size was measured before and after a test meal. Fasting gallbladder size increased with the age of the infants. However, when the size was corrected for the infant's weight, no age-related variation was found. The contraction index (CI) was determined as a percentage decrement of planimetric gallbladder size from the initial size. The mean CI declined with age from 75% (±27%) mean (±SD)) at the age of 6 weeks to 24% (±28%) at the age of 12 months. Overall CI varied from −44% to 100%. An increase in gallbladder size after the test meal was observed in 4 infants. Gallbladder volumes were also calculated, but two-dimensional measurements were regarded as more accurate in infants. A large variation was found in the size as well as in the contractility of the gallbladder in infants less than 1 year of age.

A combined gas chromatography-mass spectrometry (GC-MS) technique was used for serial determination of serum arabinitol levels in patients with postoperative candidiasis. Forty subjects were investigated, 18 patients with candidiasis, 7 patients with superficialCandida colonization and 15 postoperative control patients. The arabinitol levels were highly elevated, slightly elevated and normal in 13, 1 and 4 patients respectively with candidiasis; in 2, 2 and 3 colonized patients and in 1, 1 and 13 control patients (p<0.001,x2, between all the groups). The sensitivity of a single arabinitol determination for detection of postoperative candidiasis was 27.6 % and the specificity 89.2 %. Use of multiple samples improved sensitivity up to 72.2 % per patient (123 samples) with a specificity of 86.4 %. Highly elevated arabinitol concentrations were detected in only one patient before the onset of therapy. Determination of arabinitol levels by GC-MS is a specific test for diagnosing candidiasis, but multiple samples are required for adequate sensitivity, and the initiation of therapy must still be on an empirical basis.

Relative amounts of D-arabinitol (fungal origin) and L-arabinitol (part of normal human metabolism) in urine were determined by gas chromatography and mass spectrometry from 61 hospitalized patients with hematological malignancies. Seventeen neutropenic patients with acute leukemia (with 53 samples) had disseminated yeast infections and received empiric antifungal therapy before confirmation of the diagnosis. Control groups consisted of 22 hematologic patients (76 samples) with either mucosal (n = 10) or urinary (n = 12) Candida colonization and 22 neutropenic patients (34 samples) with no clinical or laboratory signs of invasive yeast infection. Reference values were also obtained from 50 healthy adults (50 samples). The mean urine D-arabinitol/L-arabinitol ratio +/- standard deviation (range) was 16.91 +/- 41.79 (1.41 to 254.75) in patients with disseminated infection, 2.73 +/- 2.48 (1.11 to 19.00) in colonized hematologic patients, 2.12 +/- 0.84 (1.16 to 5.84) in neutropenic controls, and 1.95 +/- 0.34 (0.97 to 3.44) in healthy adults (P < 0.001 between patients with disseminated infection and all control groups). The sensitivity and specificity of the assay for detecting disseminated yeast infection were, respectively, 88 and 91% per patient (upper limit of normal, 4.00). Seventy-one percent of patients already expressed elevated values at the onset of empiric antifungal therapy. The diagnosis of disseminated infection was confirmed on average 21.7 days after the first elevation of the D-arabinitol/L-arabinitol ratio. The method contributes to diagnosis of disseminated yeast infection and helps in monitoring patients at risk, to support the initiation of antifungal therapy at an early stage of the disease.

Objective: Levosimendan in a new inodilator drug that sensitises troponin C in heart muscle cells to calcium, thus improving contractility. In previous studies, a single 2 mg intravenous dose of levosimendan increased cardiac output (CO) in healthy volunteers by about 40% and decreased pulmonary capillary wedge pressure in heart failure patients by 40–50%.

(BMJ. 2019;367:1–11)The occurrence of infants born <28 weeks gestation is rare in both the United Kingdom and the United States, but such incidents carry a very high risk of death, neonatal morbidity, and long-term disability. Previous research has indicated that the best outcomes for these infants are achieved when care is given in specialized tertiary hospitals. At-risk pregnant women who present at nontertiary hospitals are often transferred to more specialized facilities either before or after delivery; a number of recent studies have focused on the outcomes of infants who were transferred postnatally, with inconclusive results. These investigators conducted their research to determine if transferred infants had a higher incidence of mortality and severe brain injury compared with nontransferred infants born in tertiary hospitals.

Moderate to severe papulopustular acne requires systemic and long-term treatment, the first choice therapy most often being tetracycline. In this double-blind randomized parallel-group study a new erythromycin derivative, erythromycin acistrate (EA), a 2'-acetyl ester prodrug of erythromycin, was compared with routine tetracycline treatment. The study group comprised 60 patients with moderate or severe acne who were treated for up to 6 months. One patient in each treatment group was completely cured within the first 3 months. After 6 months' treatment a further patient in the tetracycline group was completely cured. There were no significant changes in laboratory test values. Both drugs were well tolerated: one patient in each treatment group discontinued treatment due to diarrhoea during the first week. EA is a safe and well-tolerated alternative to tetracycline for the systemic treatment of acne.

Presence of muramic acid (as a marker for bacterial cell wall peptidoglycan) was analysed by gas chromatography and mass spectrometry in the peripheral blood leucocytes of subjects from a range of ages (9-80 years) and groups (healthy individuals, patients with rheumatoid arthritis, osteoarthrosis, essential hypertension or multiple sclerosis). Sixty per cent of the sample from the youngest subjects contained detectable muramic acid. The percentage of people with circulating leucocytes containing muramic acid decreased gradually with age, being less than 5% in all groups over 40 years. No clear correlation between the presence of muramic acid and the disease was observed.

Background: Single course of BM decreases neonatal morbidity when administrated within 7 days before preterm delivery. The benefits of second course of BM are unknown.Aims: To evaluate the efficacy of second course of BM in increasing the intact survival of preterm infants.Methods: In this randomized, blinded trial, pregnant women (before 34.0 gestational weeks) were eligible if they had remained undelivered more than 7 days after antenatal BM. Single dose of BM (12 mg) or placebo was given, when the preterm delivery was anticipated. Primary outcome was intact survival without respiratory distress syndrome and/or intracerebral hemorrhage (grade 3–4).Results: 251 mothers participated the study. All infants were delivered prior to 35 weeks of gestation. At present the outcome of 285 infants has been analyzed. The intact survival was 48% in BM and 58% in placebo groups (P=0.1). The intact survival was non-significantly higher in BM group (58% vs. 41%, P=0.3), when the study drug was administered more than 24 h before birth (group 1). The incidence of intact survival was lower in BM group (44% vs. 61%, P=0.01), when the intervention took place less than 24 h before birth (group 2). In group 1, the risk of patent ductus arteriosus was 16% in BM and 41% in placebo group (P=0.04), vs. 29% and 27% in group 2. In group 2, systolic and diastolic blood pressures were increased in BM arm (P=0.02 and P=0.03). In group 1, blood pressure levels were similar between study groups. The second course of BM did not influence the acute outcome of preterm infants. The preterm infants benefited from antenatal BM, when treatment was given more than 24 h before delivery. BM given less than 24 hours before delivery was associated with increased blood pressure after birth and with a decrease in intact survival.