A systematic review and meta-analysis of the clinimetric properties of the core outcome measurement instruments for clinical effectiveness trials of nutritional and metabolic interventions in critical illness (CONCISE).

BACKGROUND: CONCISE is an internationally agreed minimum set of outcomes for use in nutritional and metabolic clinical research in critically ill adults. Clinicians and researchers need to be aware of the clinimetric properties of these instruments and understand any limitations to ensure valid and reliable research. This systematic review and meta-analysis were undertaken to evaluate the clinimetric properties of the measurement instruments identified in CONCISE. METHODS: Four electronic databases were searched from inception to December 2022 (MEDLINE via Ovid, EMBASE via Ovid, CINAHL via Healthcare Databases Advanced Search, CENTRAL via Cochrane). Studies were included if they examined at least one clinimetric property of a CONCISE measurement instrument or recognised variation in adults ≥ 18 years with critical illness or recovering from critical illness in any language. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist for systematic reviews of Patient-Reported Outcome Measures was used. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses were used in line with COSMIN guidance. The COSMIN checklist was used to evaluate the risk of bias and the quality of clinimetric properties. Overall certainty of the evidence was rated using a modified Grading of Recommendations, Assessment, Development and Evaluation approach. Narrative synthesis was performed and where possible, meta-analysis was conducted. RESULTS: A total of 4316 studies were screened. Forty-seven were included in the review, reporting data for 12308 participants. The Short Form-36 Questionnaire (Physical Component Score and Physical Functioning), sit-to-stand test, 6-m walk test and Barthel Index had the strongest clinimetric properties and certainty of evidence. The Short Physical Performance Battery, Katz Index and handgrip strength had less favourable results. There was limited data for Lawson Instrumental Activities of Daily Living and the Global Leadership Initiative on Malnutrition criteria. The risk of bias ranged from inadequate to very good. The certainty of the evidence ranged from very low to high. CONCLUSIONS: Variable evidence exists to support the clinimetric properties of the CONCISE measurement instruments. We suggest using this review alongside CONCISE to guide outcome selection for future trials of nutrition and metabolic interventions in critical illness. TRIAL REGISTRATION: PROSPERO (CRD42023438187). Registered 21/06/2023.

Core outcome measures for clinical effectiveness trials of nutritional and metabolic interventions in critical illness: an international modified Delphi consensus study evaluation (CONCISE).

BACKGROUND: Clinical research on nutritional and metabolic interventions in critically ill patients is heterogenous regarding time points, outcomes and measurement instruments used, impeding intervention development and data syntheses, and ultimately worsening clinical outcomes. We aimed to identify and develop a set of core outcome domains and associated measurement instruments to include in all research in critically ill patients. METHODS: An updated systematic review informed a two-stage modified Delphi consensus process (domains followed by instruments). Measurement instruments for domains considered 'essential' were taken through the second stage of the Delphi and a subsequent consensus meeting. RESULTS: In total, 213 participants (41 patients/caregivers, 50 clinical researchers and 122 healthcare professionals) from 24 countries contributed. Consensus was reached on time points (30 and 90 days post-randomisation). Three domains were considered 'essential' at 30 days (survival, physical function and Infection) and five at 90 days (survival, physical function, activities of daily living, nutritional status and muscle/nerve function). Core 'essential' measurement instruments reached consensus for survival and activities of daily living, and 'recommended' measurement instruments for physical function, nutritional status and muscle/nerve function. No consensus was reached for a measurement instrument for Infection. Four further domains met criteria for 'recommended,' but not 'essential,' to measure at 30 days post-randomisation (organ dysfunction, muscle/nerve function, nutritional status and wound healing) and three at 90 days (frailty, body composition and organ dysfunction). CONCLUSION: The CONCISE core outcome set is an internationally agreed minimum set of outcomes for use at 30 and 90 days post-randomisation, in nutritional and metabolic clinical research in critically ill adults.

Cesarean section increases the risk of respiratory adaptive disorders in healthy late preterm and two groups of mature newborns.

The rates of delivery by Cesarean section (CS) have been trending upwards in recent decades, perhaps leading to higher rates of dysfunction in respiratory adaptation in newborns. We present epidemiological data for pulmonary adaptation by mode of delivery for healthy late preterm and term infants born at a regional tertiary care center. The overall CS rate was 22% with the largest proportion of these in late preterms (39%). This drops to 30% in infants born after 37 weeks gestation and to 11% for those born after 40 weeks. Infants needing respiratory support decreased significantly as gestational age increased: 88% at 34 weeks, 67% at 35 weeks, 28% at 36 weeks, 17% at 37 weeks and 8% at 40 weeks. The risk of respiratory morbidity following CS as compared to vaginal delivery (VD) was substantially higher. 50% of infants born by CS needed respiratory support compared to only 12% following VD. 82% of all late preterm infants born by CS developed respiratory morbidity compared to 36% following VD. Comparable data for infants born after 37 and 40 weeks gestation were 33% compared to 9% and 26% compared to 6% respectively. Late preterm infants born after 36 weeks gestation showed the most marked difference by mode of birth with 66% needing respiratory support following CS as compared to only 9% following VD. Our data could be useful in counselling parents about risk associated with delivery by Cesarean section. A critical view should be taken of increasing CS rates worldwide because of a clear correlation in increased morbidity in infants, especially late preterm infants.

Definition, prevalence, and outcome of feeding intolerance in intensive care: a systematic review and meta-analysis.

Clinicians and researchers frequently use the phrase 'feeding intolerance' (FI) as a descriptive term in enterally fed critically ill patients. We aimed to: (1) determine what is the most accepted definition of FI; (2) estimate the prevalence of FI; and (3) evaluate whether FI is associated with important outcomes. Systematic searches of peer-reviewed publications using PubMed, MEDLINE, and Web of Science were performed with studies reporting FI extracted. We identified 72 studies defining FI. In 33 studies, the definition was based on large gastric residual volumes (GRVs) together with other gastrointestinal symptoms, while 30 studies relied solely on large GRVs, six studies used inadequate delivery of enteral nutrition (EN) as a threshold, and three studies gastrointestinal symptoms without reference to GRV. The median volume used to define a 'large' GRV was 250 ml (ranges from 75 to 500 ml). The pooled proportion (n = 31 studies) of FI was 38.3% (95% CI 30.7-46.2). Five studies reported outcomes, all of them observed adverse outcome in FI patients. In three studies, respectively, FI was associated with increased mortality and ICU length-of-stay. In summary, FI is inconsistently defined but appears to occur frequently. There are preliminary data indicating that FI is associated with adverse outcomes. A standard definition of FI is required to determine the accuracy of these preliminary data.

[Prediction of extubation failure in ELBW preterm infants]. / Prädiktion von Extubationsversagen bei ELBW-Frühgeborenen.

BACKGROUND: The accurately timed extubation of ventilated ELBW preterm infants is still a problem. With different data systems the attempt has been made to more accurately predict the successful extubation of these infants. However, there do not yet exist any satisfying solutions. PATIENTS/METHODS: We retrospectively analysed 66 ELBW preterm infants who were endotracheal intubated and ventilated within 24 h postnatal. Basic data, clinical and ventilation data immediately before planned extubation and in several intervals during the following 24 h, as well as outcome variables at discharge were interpreted. RESULTS: 51 patients were successfully extubated (EE-group), 15 (22.7%) failed extubation (reintubation within 48 h after extubation, EV-group). Immediately before extubation in the EE-group there was found a significantly higher inspiratory oxygen concentration (FiO2) in comparison to the EV-group (0.25 vs. 0.3; p=0.01). After the extubation attempt the inspiratory oxygen concentration stayed lower in the EE-group, whereas in the EV-group it rose remarkably (2 h after ext.: 0.26 vs. 0.4; p<0.001). Neither of the basic data showed any significant difference. The outcome analysis indicated a longer intensive care in the EV-group and a trend towards increased BPD and ROP. CONCLUSION: The study shows that for ELBW preterm infants the inspiratory oxygen concentration is especially important to predict a successful extubation. According to our data, the inspiratory oxygen demand before and immediately after extubation establishes the essential difference between successfully extubated and reintubated infants.

Risk factors for intra-abdominal hypertension in mechanically ventilated patients.

BACKGROUND: Intra-abdominal hypertension (IAH) in intensive care patients is associated with an adverse outcome, but the risk factors for development of IAH have not been extensively studied. We aimed to identify independent risk factors for IAH in mechanically ventilated (MV) patients. METHODS: In this prospective observational study, 563 MV patients staying in the general intensive care unit (ICU) of a university hospital for more than 24 h were observed during their ICU stay. Repeated intermittent measurements of intra-abdominal pressure (IAP) via the urinary bladder were performed. RESULTS: IAH (sustained or repeated IAP≥12 mmHg) developed in 182 patients (32.3%). From all the study patients, 44.4% had a primary pathology in the abdomino-pelvic region. Two thirds of all IAH cases developed in this group. Obesity [body mass index (BMI)>30], high positive end-expiratory pressure (PEEP>10), respiratory failure (PaO(2)/FiO(2) <300), use of vasopressors/inotropes, pancreatitis, hepatic failure/cirrhosis with ascites, gastrointestinal bleeding and laparotomy on admission day were identified as independent risk factors for IAH. None of the patients without any of these risk factors (26 patients) developed IAH. CONCLUSION: The precise prediction of development IAH in mixed ICU population remains difficult. In the absence of BMI>30, PEEP>10 cmH(2)O, PaO(2)/FiO(2) <300, use of vasopressors/inotropes, pancreatitis, hepatic failure/cirrhosis with ascites, gastrointestinal bleeding and laparotomy on admission day, the risk for development of IAH in MV ICU patients is minimal.

Prevalence of hypophosphatemia in the ICU - Results of an international one-day point prevalence survey.

BACKGROUND & AIMS: Hypophosphatemia (HypoP) is associated with organ dysfunction and mortality. Despite its potential severe consequences, HypoP remains poorly characterized in terms of real prevalence and timing of onset. The primary objective was to determine the prevalence of HypoP defined as blood phosphate <0.8 and < 0.65 mmol/l on one particular day at international level. METHODS: One-day point prevalence survey conducted by the Section of Metabolism, Endocrinology and Nutrition (MEN) of the European Society of Intensive Care Medicine (ESICM) during week 11-2020. RESULTS: In total, 56 adult and 4 paediatric ICUs, from 22 countries participated: 41 ICUs were mixed medico surgical, the 19 others being cardiac, medical or surgical. Phosphate measurements were performed daily in 21 ICUs, and 1-3 times per week in 39 ICUs. On D-Day 909 patients (883 adults) were present and 668/883 (75.7%) had serum/plasma phosphate determined, revealing a HypoP in 103 (15.4%) patients aged 62 [18 to 85] years. Of those, 49 patients presented phosphate <0.65 mmol/l: cases of hypophosphatemia were detected at any time of patient's ICU stay. No HypoP was observed in children. A treatment protocol existed only in 41.1% of adult ICUs, independently of ICU type, or size. Only 41/98 of the HypoP patients (29/41 of patients with phosphate <0.65 mmol/l) were receiving phosphate. CONCLUSION: HypoP is present at least in 15.4% of ICU patients, and may occur at any time during the ICU stay. The absence of phosphate repletion protocols in 60% of participating ICUs is an unexpected finding, and confirms the necessity for the development of ICU phosphate protocols and guidelines. CLINICALTRIALS IDENTIFIER: NCT04201899.

A Degrading Potassium Tablet Mimicking Active Gastric Bleeding in a Computer Tomographic Investigation.

A 54-year-old male patient was admitted to the hospital due to symptoms caused by an intramural hematoma of the descending aorta. In a contrast media-enhanced computed tomography scan performed five days after admission to evaluate dynamics of the hematoma, a hyperdense lesion was seen in the stomach. A suspicion of gastric hemorrhage was raised at the first evaluation. Because the patient's clinical condition and hemoglobin levels were stable, gastroscopy to rule out an aorto-gastric fistula or another type of bleeding was not undertaken. In the secondary evaluation of the history and images, it became clear that the hyperdense lesion mimicking bleeding in the stomach must have been caused by a degrading potassium tablet ingested by the patient five hours before the investigation.

BCA-1 is highly expressed in Helicobacter pylori-induced mucosa-associated lymphoid tissue and gastric lymphoma.

Infection with Helicobacter pylori (Hp) induces the formation of lymphoid tissue in the stomach and the occasional development of primary gastric B-cell lymphomas. We have studied the expression of 2 chemokines that attract B lymphocytes, BCA-1 and SLC, in gastric tissue samples obtained from patients with chronic gastritis induced by Hp infection or nonsteroidal anti-inflammatory drugs, as well as from patients with Hp-associated low-grade and high-grade gastric lymphomas. High-level expression of BCA-1 and its receptor, CXCR5, was observed in all mucosal lymphoid aggregates and in the mantle zone of all secondary lymphoid follicles in Hp-induced gastric mucosa-associated lymphoid tissue (MALT). Follicular dendritic cells and B lymphocytes are possible sources of BCA-1, which is not expressed by T lymphocytes, macrophages, or CD1a(+) dendritic cells. Strong expression of BCA-1 and CXCR5 was also detected in the transformed B cells of gastric MALT lymphomas. By contrast, SLC was confined almost exclusively to endothelial cells in and outside the lymphoid tissue. Only scant, occasional SLC expression was observed in the marginal zone of MALT follicles. Our findings indicate that BCA-1, which functions as a homing chemokine in normal lymphoid tissue, is induced in chronic Hp gastritis and is involved in the formation of lymphoid follicles and gastric lymphomas of the MALT type.

Stereoselective inhibition of alpha-L-fucosidases by N-benzyl aminocyclopentitols.

[structure: see text] (1R,2R,3R,4R,5R)-4-Amino-5-methylcyclopentane-1,2,3 -tr iol 8, its 4S stereoisomer 9, and their acyclic analogues (R)- and (S)-2-aminobutanol 11 and 12 are selective but moderate inhibitors of alpha-L-fucosidases. N-Benzylation selectively enhances inhibition potency for aminocyclopentitol 8 (--> 1, K(i) = 6.8 x 10(-)(7) M) but decreases inhibition for its 4S-stereoisomer 9 (--> 2, K(i) = 1.1 x 10(-)(4) M) and for the aminobutanols 11 (--> 13, no inhibition) and 12 (--> 14, no inhibition).

Synthesis and evaluation of aminocyclopentitol inhibitors of beta-glucosidases.

[reaction: see text] (1R,2S,3S,4R,5R)-4-Amino-5-(hydroxymethyl)cyclopentane-1,2,3-triol 1, prepared from D-glucose, inhibits beta-glucosidases from Caldocellum saccharolyticum (Ki = 1.8 x 10(-7) M) and from almonds (Ki = 3.4 x 10(-6) M). Inhibition is not influenced by N-ethylation (--> 15) but is strongly reduced upon N-acetylation (--> 12). Inversion of stereochemistry at C(5) (--> 14) has little effect on inhibition of beta-glucosidases. These experiments suggest that 1 acts as an analogue of a protonated beta-glucoside.

Components of the clinician's confidence.

Judgmental tasks in person perception are related to the degree of confidence of the performing clinician. 10 judges were exposed to increments of video and/or case history information about 10 patients and were asked to rate the patients' characteristics after each phase as well as to indicate how confident they felt about their ratings. The results suggest that the level of confidence varies according to the information available (as found in other research). the item judged, and the personality of the judge. The impact of the mode of information did not become sufficiently clear.

[Henry E. Sigerist: creation of medical historical study. An unpublished manuscript in the Zurich medical history institute]. / Henry E. Sigerist: Die Gestaltung des medizinhistorischen Unterrichts. Ein unpubliziertes Manuskript im Zürcher Medizinhistorischen Institut.

In 1951 Henry E. Sigerist (1891-1957) wrote a manuscript paper on the structure of lectures on medical history. In this paper, which has remained unpublished yet, Sigerist's considerations are based on many years of experience in teaching in Leipzig and Baltimore. According to him, a lively medical history must always refer to current medicine. Furthermore, it should try to bridge the gulf between the arts, the social and the natural sciences. His proposal for a possible schedule includes an introductory course of lectures into medicine for beginners and a course on the history of medicine for advanced students. Lectures on medical ethics and sociology of medicine are also part of his programme. Finally, Sigerist stresses the fact that, in addition to these four lecture courses, seminars and a colloquy may provide students with the possibility of working on a specific subject in more detail.

A systematic review and individual patient data meta-analysis on intra-abdominal hypertension in critically ill patients: the wake-up project. World initiative on Abdominal Hypertension Epidemiology, a Unifying Project (WAKE-Up!).

Intra-abdominal hypertension (IAH), defined as a pathologically increase in intraabdominal pressure, is commonly found in critically ill patients. While IAH has been associated with several abdominal as well as extra-abdominal conditions, few studies have examined the occurrence of IAH in relation to mortality. The aim of this paper was to evaluate the prognostic role of IAH and its risk factors at admission in critically ill patients across a wide range of settings and countries. An individual patient meta-analysis of all available data and a systematic review of published (in full or as abstract) medical databases and studies between 1996 and June 2012 were performed. The search was limited to "clinical trials" and "randomized controlled trials", "adults", using the terms "intra-abdominal pressure", "intraabdominal hypertension" combined with any of the terms "outcome" and "mortality". All together data on 2707 patients, representing 21 centers from 11 countries was obtained. Data on 1038 patients were not analysed because of the following exclusion criteria: no IAP value on admission (N.=712), absence of information on ICU outcome (N.=195), age <18 or >95 years (N.=131). Data from 1669 individual patients (19 centers from 9 countries) were analyzed in the meta-analysis. Presence of IAH was defined as a sustained increase in IAP equal to or above 12 mmHg. At admission the mean overall IAP was 9.9±5.0 mmHg, with 463 patients (27.7%) presenting IAH with a mean IAP of 16.3±3.4 mmHg. The only independent predictors for IAH were SOFA score and fluid balance on the day of admission. Five hundred thirteen patients (30.8%) died in intensive care. The independent predictors for intensive care mortality were IAH, SAPS II score, SOFA score and admission category. This systematic review and individual patient data meta-analysis shows that IAH is frequently present in critically ill patients and it is an independent predictor for mortality.

Changes in regional tissue oxygenation saturation and desaturations after red blood cell transfusion in preterm infants.

OBJECTIVE: The study investigated the ability of near-infrared spectroscopy (NIRS) to detect subgroups of preterm infants who benefit most from red blood cell (RBC) transfusion in regard to cerebral/renal tissue oxygenation (i) and the number of general oxygen desaturation below 80% (SaO(2) <80%) (ii). STUDY DESIGN: Cerebral regional (crSO(2)) and peripheral regional (prSO(2)) NIRS parameters were recorded before, during, immediately after and 24 h after transfusion in 76 infants. Simultaneously, SaO(2) <80% were recorded by pulse oximetry. To answer the basic question of the study, all preterm infants were divided into two subgroups according to their pretransfusion crSO(2) values (<55% and ≥55%). This cutoff was determined by a k-means clustering analysis. RESULT: crSO(2) and prSO(2) increased significantly in the whole study population. A stronger increase (P<0.0005) of both was found in the subgroup with pretransfusion crSO(2) values <55%. Regarding the whole population, a significant decrease (P<0.05) of episodes with SaO(2) <80% was observed. The subgroup with crSO(2) baselines <55% had significant (P<0.05) more episodes with SaO(2) <80% before transfusion. During and after transfusion, the frequency of episodes with SaO(2) <80% decreased more in this group compared with the group with crSO(2) baselines ≥55%. CONCLUSION: NIRS measurement is a simple, non-invasive method to monitor regional tissue oxygenation and the efficacy of RBC transfusion. Infants with low initial NIRS values benefited most from blood transfusions regarding SaO(2) <80%, which may be important for their general outcome.

A Systematic Review And Individual Patient Data Meta-Analysis On Intraabdominal Hypertension In Critically Ill Patients: The Wake-Up Project World Initiative on Abdominal Hypertension Epidemiology, a Unifying Project (WAKE-Up!).

Background: Intraabdominal hypertension (IAH), defined as a pathologically increase in intraabdominal pressure, is commonly found in critically ill patients. While IAH has been associated with several abdominal as well as extra-abdominal conditions, few studies have examined the occurrence of IAH in relation to mortality. Objective: To evaluate the prognostic role of IAH and its risk factors at admission in critically ill patients across a wide range of settings and countries. Data sources: An individual patient meta-analysis of all available data and a systematic review of published (in full or as abstract) medical databases and studies between 1996 and June 2012 were performed. The search was limited to "clinical trials" and "randomized controlled trials", "adults", using the terms "intraabdominal pressure", "intraabdominal hypertension" combined with any of the terms "outcome" and "mortality". All together data on 2707 patients, representing 21 centers from 11 countries was obtained. Data on 1038 patients were not analysed because of the following exclusion criteria: no IAP value on admission (n=712), absence of information on ICU outcome (n=195), age <18 or > 95 years (n=131). Results: Data from 1669 individual patients (19 centers from 9 countries) were analyzed in the meta-analysis. Presence of IAH was defined as a sustained increase in IAP equal to or above 12 mmHg. At admission the mean overall IAP was 9.9±5.0 mmHg, with 463 patients (27.7%) presenting IAH with a mean IAP of 16.3±3.4 mmHg. The only independent predictors for IAH were SOFA score and fluid balance on the day of admission. Five hundred thirteen patients (30.8%) died in intensive care. The independent predictors for intensive care mortality were IAH, SAPS II score, SOFA score and admission category. Conclusions: This systematic review and individual patient data meta-analysis shows that IAH is frequently present in critically ill patients and it is an independent predictor for mortality.

Early enteral nutrition in critically ill patients: ESICM clinical practice guidelines

PURPOSE: To provide evidence-based guidelines for early enteral nutrition (EEN) during critical illness. METHODS: We aimed to compare EEN vs. early parenteral nutrition (PN) and vs. delayed EN. We defined "early" EN as EN started within 48 h independent of type or amount. We listed, a priori, conditions in which EN is often delayed, and performed systematic reviews in 24 such subtopics. If sufficient evidence was available, we performed meta-analyses; if not, we qualitatively summarized the evidence and based our recommendations on expert opinion. We used the GRADE approach for guideline development. The final recommendations were compiled via Delphi rounds. RESULTS: We formulated 17 recommendations favouring initiation of EEN and seven recommendations favouring delaying EN. We performed five meta-analyses: in unselected critically ill patients, and specifically in traumatic brain injury, severe acute pancreatitis, gastrointestinal (GI) surgery and abdominal trauma. EEN reduced infectious complications in unselected critically ill patients, in patients with severe acute pancreatitis, and after GI surgery. We did not detect any evidence of superiority for early PN or delayed EN over EEN. All recommendations are weak because of the low quality of evidence, with several based only on expert opinion. CONCLUSIONS: We suggest using EEN in the majority of critically ill under certain precautions. In the absence of evidence, we suggest delaying EN in critically ill patients with uncontrolled shock, uncontrolled hypoxaemia and acidosis, uncontrolled upper GI bleeding, gastric aspirate >500 ml/6 h, bowel ischaemia, bowel obstruction, abdominal compartment syndrome, and high-output fistula without distal feeding access.

[Drug withdrawal in newborns - clinical data of 49 infants with intrauterine drug exposure: what should be done?]. / Drogenentzug beim Neugeborenen - klinische und soziodemografische Daten von 49 Neugeborenen drogenabhängiger Mütter: Was kann und soll getan werden?

BACKGROUND: Infants of drug abusing mothers are at high risk to suffer from neonatal abstinence syndrome (NAS). Depending on the drug signs of neonatal withdrawal vary but mainly include central nervous system irritability. NAS causes long duration of hospital stay. Severe withdrawal signs are seen in infants exposed to methadone, infants exposed to other opioids like heroin or buprenorphine have been shown to be less symptomatic. Between the years 1997 and 2003 following the border opening there was a dramatic increase in drug exposed newborns seen in the area of Leipzig (East Germany). METHODS: In a retrospective study maternal and infant characteristics, severity of symptoms, duration of withdrawal and hospital stay, duration and kind of treatment as well as modalities for release from hospital were analyzed. RESULTS: From 1997 to 2003 49 drug exposed newborns were admitted to our neonatal care unit. There was an increase of the number of affected infants within these years ( ). Maternal drug abuse (n=48) included mainly methadone (n=33), in second line heroine and benzodiazepines, in a few cases also cocaine and cannabinoides. 3 mothers received substitution therapy with buprenorphine. Additional drug use to substitution therapy was seen in 15 mothers. Drugs of abuse were detected in infant urine specimen (36/48). 35 of exposed newborns showed signs of NAS (incidence of NAS 71%). For evaluation of withdrawal signs and conduction of therapy the Finnegan score was used. As first line pharmacological treatment phenobarbitone was administered (n=42), secondary morphine was used (n=14, treatment failure 33%). Mean duration of hospital stay was 21 days. Mean duration of pharmacological treatment was 14 days with longer duration for methadone exposed infants vs. non-methadone exposed infants (16 vs. 10 days). Hospital stay was longer for non-methadone exposed infants. Maternal intake of more than 20 mg methadone per day vs. up to 20 mg per day caused longer duration of hospital stay (28 vs. 20 days, p=0,015). CONCLUSION: Long duration of hospital stay and pharmacological treatment call for optimised principal guide lines for diagnosis, treatment and long term follow-up. The results also underline the need for further research for an effective pharmacological treatment.