Effect of exercise after a deep venous thrombosis: A systematic review.

Post-thrombotic syndrome (PTS) is a common complication after deep vein thrombosis (DVT) and has a major impact on physical symptoms, quality of life (QoL) and economic costs. Relatively simple lifestyle interventions as physical exercise might reduce PTS severity and increase QoL. To evaluate the direct and long-term effects of physical activity in patients with an acute or previous DVT. We conducted a systematic review through an additional search from 2007 up to March 2022, to complement the comprehensive systematic review of Kahn et al. Articles evaluating the effect of exercise after a DVT including symptoms, QoL and the incidence and severity of PTS, were included. Quality of the studies was assessed using a GRADE-like checklist and results were reported according to the PRISMA Statement. Ten studies were included, seven randomized controlled trials and three cohort studies. We identified three types of physical activity based on timing and duration; (1) early mobilisation in the acute phase of the DVT; (2) short duration exercise 1 year after DVT and (3) prolonged exercise during follow-up after a previous DVT. Early mobilisation showed improvement in QoL and pain reduction and after 2 years it resulted in a significant reduction of PTS severity. Prolonged supervised exercise resulted in improvement of QoL. In addition, positive effects on symptoms of venous insufficiency and muscle functions were observed. None of the included studies reported an increased risk of PTS or worsening of symptoms due to physical activity. Physical exercise after a DVT is safe, improves QoL, reduces pain and decreases PTS severity. Lifestyle intervention such as guided individualized training programs can be a useful supplementary therapy for patients after a DVT or for PTS patients. Optimal training programs may be identified by further studies that improve patient-oriented outcomes for both adults and children after a DVT.

Quantifying Quality of Reaching Movements Longitudinally Post-Stroke: A Systematic Review.

BACKGROUND: Disambiguation of behavioral restitution from compensation is important to better understand recovery of upper limb motor control post-stroke and subsequently design better interventions. Measuring quality of movement (QoM) during standardized performance assays and functional tasks using kinematic and kinetic metrics potentially allows for this disambiguation. OBJECTIVES: To identify longitudinal studies that used kinematic and/or kinetic metrics to investigate post-stroke recovery of reaching and assess whether these studies distinguish behavioral restitution from compensation. METHODS: A systematic literature search was conducted using the databases PubMed, Embase, Scopus, and Wiley/Cochrane Library up to July 1st, 2020. Studies were identified if they performed longitudinal kinematic and/or kinetic measurements during reaching, starting within the first 6 months post-stroke. RESULTS: Thirty-two longitudinal studies were identified, which reported a total of forty-six different kinematic metrics. Although the majority investigated improvements in kinetics or kinematics to quantify recovery of QoM, none of these studies explicitly addressed the distinction between behavioral restitution and compensation. One study obtained kinematic metrics for both performance assays and a functional task. CONCLUSIONS: Despite the growing number of kinematic and kinetic studies on post-stroke recovery, longitudinal studies that explicitly seek to delineate between behavioral restitution and compensation are still lacking in the literature. To rectify this situation, future studies should measure kinematics and/or kinetics during performance assays to isolate restitution and during a standardized functional task to determine the contributions of restitution and compensation.

Advanced image analytics predicting clinical outcomes in patients with colorectal liver metastases: A systematic review of the literature.

BACKGROUND: To better select patients with colorectal liver metastases (CRLM) for an optimal selection of treatment strategy (i.e. local, systemic or combined treatment) new prognostic models are warranted. In the last decade, radiomics has emerged as a field to create predictive models based on imaging features. This systematic review aims to investigate the current state and potential of radiomics to predict clinical outcomes in patients with CRLM. METHODS: A comprehensive literature search was conducted in the electronic databases of PubMed, Embase, and Cochrane Library, according to PRISMA guidelines. Original studies reporting on radiomics predicting clinical outcome in patients diagnosed with CRLM were included. Clinical outcomes were defined as response to systemic treatment, recurrence of disease, and survival (overall, progression-free, disease-free). Primary outcome was the predictive performance of radiomics. A narrative synthesis of the results was made. Methodological quality was assessed using the radiomics quality score. RESULTS: In 11 out of 14 included studies, radiomics was predictive for response to treatment, recurrence of disease, survival, or a combination of outcomes. Combining clinical parameters and radiomic features in multivariate modelling often improved the predictive performance. Different types of individual features were found prognostic. Noticeable were the contrary levels of heterogeneous and homogeneous features in patients with good response. The methodological quality as assessed by the radiomics quality score varied considerably between studies. CONCLUSION: Radiomics appears a promising non-invasive method to predict clinical outcome and improve personalized decision-making in patients with CRLM. However, results were contradictory and difficult to compare. Standardized prospective studies are warranted to establish the added value of radiomics in patients with CRLM.

Exocrine pancreatic insufficiency after esophagectomy: a systematic review of literature.

Complaints of maldigestion, malabsorption, and unintended weight loss after esophagectomy are often attributed to an impaired exocrine pancreatic function. This review systematically summarizes all literature reporting on the presence of exocrine pancreatic insufficiency (EPI) after esophagectomy and the effect of treatment with pancreatic enzymes on gastrointestinal complaints, body weight, and quality of life. Databases of PubMed, Embase, and Wiley/Cochrane Library were searched systematically until July 2020. Studies reporting on EPI and pancreatic enzyme replacement therapy after esophagectomy were included. The Newcastle-Ottawa scale was used to assess study quality. Four studies, including 158 patients, were selected. The maximum score for study quality was six (range 4-6). Exocrine pancreatic function was investigated in three studies, measured by fecal elastase-1 and 72-hour fecal fat excretion. Fecal elastase-1 levels <200 µg/g were reported in 16% of patients at 4 months, 18% at 6 months, and 31% at 18-24 months postoperatively. A decreased fecal fat absorption was noticed in 57% 1 month postoperatively. Treatment with pancreatic enzymes was reported in two studies. In patients with fecal elastase-1 levels <200 µg/g, 90% of patients reported improvement in symptoms and 70% reported improvement in weight. In patients with complaints of steatorrhea, 87% noticed settlement of symptoms. Based on current literature, complaints of maldigestion, malabsorption, and unintended weight loss after esophagectomy are common and can be related to an impaired exocrine pancreatic function. High-quality studies evaluating the presence of EPI and the effect of treatment with pancreatic enzymes after esophagectomy are needed to verify this conclusion.

Treatment of paraesophageal hiatal hernia in octogenarians: a systematic review and retrospective cohort study.

Over the coming years octogenarians will make up an increasingly large proportion of the population. With the rise in octogenarians more paraesophageal hiatal hernias may be identified. In research for the optimal treatment for paraesophageal hiatal hernias, octogenarians are often omitted and the optimal surgical strategy for this patient group remains unclear. A systematic search in PubMed, Embase, and The Cochrane Library was conducted, including articles compromising 'surgery,' 'paraesophageal hiatal hernia,' and 'octogenarians.' Selection of articles was based on independent review by two authors. Alongside, a retrospective cohort study was conducted including all type II-IV hiatal hernia repairs performed in the VU Medical Center in Amsterdam, The Netherlands, from 2005 to 2015. A total of 486 papers were eligible for selection. After careful selection, a total of eight articles were included. All articles were retrospective cohort studies describing different proportions of octogenarians. The populations and surgical techniques were very heterogeneous. Elective paraesophageal hiatal hernia repair was performed safely in symptomatic octogenarians in all studies. Additional analysis of 84 patients, of which 9.5% octogenarians, was performed at our tertiary referral center. A larger hernia type, more acute interventions and a higher morbidity and mortality rate was observed in octogenarians compared to patients aged <80 years. In conclusion, elective paraesophageal hiatal hernia repair can be performed in octogenarians, especially in patients without comorbidity. Findings suggest improvement in symptoms in short-term follow up, with minimal morbidity and mortality. With regard to surgical techniques, laparoscopy and fundoplication were performed safely. Octogenarians need to be included in future clinical trials to further evaluate the optimal surgical intervention. Preoperative risk assessment by clinical prediction rules should guide operative intervention, in order to evaluate risks and benefits in this challenging population.

Repeatability of quantitative 18F-FLT uptake measurements in solid tumors: an individual patient data multi-center meta-analysis.

INTRODUCTION: 3'-deoxy-3'-[18F]fluorothymidine (18F-FLT) positron emission tomography (PET) provides a non-invasive method to assess cellular proliferation and response to antitumor therapy. Quantitative 18F-FLT uptake metrics are being used for evaluation of proliferative response in investigational setting, however multi-center repeatability needs to be established. The aim of this study was to determine the repeatability of 18F-FLT tumor uptake metrics by re-analyzing individual patient data from previously published reports using the same tumor segmentation method and repeatability metrics across cohorts. METHODS: A systematic search in PubMed, EMBASE.com and the Cochrane Library from inception-October 2016 yielded five 18F-FLT repeatability cohorts in solid tumors. 18F-FLT avid lesions were delineated using a 50% isocontour adapted for local background on test and retest scans. SUVmax, SUVmean, SUVpeak, proliferative volume and total lesion uptake (TLU) were calculated. Repeatability was assessed using the repeatability coefficient (RC = 1.96 × SD of test-retest differences), linear regression analysis, and the intra-class correlation coefficient (ICC). The impact of different lesion selection criteria was also evaluated. RESULTS: Images from four cohorts containing 30 patients with 52 lesions were obtained and analyzed (ten in breast cancer, nine in head and neck squamous cell carcinoma, and 33 in non-small cell lung cancer patients). A good correlation was found between test-retest data for all 18F-FLT uptake metrics (R2 ≥ 0.93; ICC ≥ 0.96). Best repeatability was found for SUVpeak (RC: 23.1%), without significant differences in RC between different SUV metrics. Repeatability of proliferative volume (RC: 36.0%) and TLU (RC: 36.4%) was worse than SUV. Lesion selection methods based on SUVmax ≥ 4.0 improved the repeatability of volumetric metrics (RC: 26-28%), but did not affect the repeatability of SUV metrics. CONCLUSIONS: In multi-center studies, differences ≥ 25% in 18F-FLT SUV metrics likely represent a true change in tumor uptake. Larger differences are required for FLT metrics comprising volume estimates when no lesion selection criteria are applied.

Decision support systems for incurable non-small cell lung cancer: a systematic review.

BACKGROUND: Individually tailored cancer treatment is essential to ensure optimal treatment and resource use. Treatments for incurable metastatic non-small cell lung cancer (NSCLC) are evolving rapidly, and decision support systems (DSS) for this patient population have been developed to balance benefits and harms for decision-making. The aim of this systematic review was to inventory DSS for stage IIIB/IV NSCLC patients. METHODS: A systematic literature search was performed in Pubmed, Embase and the Cochrane Library. DSS were described extensively, including their predictors, model performances (i.e., discriminative ability and calibration), levels of validation and user friendliness. RESULTS: The systematic search yielded 3531 articles. In total, 67 articles were included after additional reference tracking. The 39 identified DSS aim to predict overall survival and/or progression-free survival, but give no information about toxicity or cost-effectiveness. Various predictors were incorporated, such as performance status, serum and inflammatory markers, and patient and tumor characteristics. Some DSS were developed for the entire incurable NSCLC population, whereas others were specifically for patients with brain or spinal metastases. Few DSS had been validated externally using recent clinical data, and the discrimination and calibration were often poor. CONCLUSIONS: Many DSS have been developed for incurable NSCLC patients, but DSS are still lacking that are up-to-date with a good model performance, while covering the entire treatment spectrum. Future DSS should incorporate genetic and biological markers based on state-of-the-art evidence, and compare multiple treatment options to estimate survival, toxicity and cost-effectiveness.

Systematic Review of Exocrine Pancreatic Insufficiency after Gastrectomy for Cancer.

BACKGROUND: Survival rates after a total gastrectomy with adequate lymphadenectomy are improving, leading to a shift in outcomes of interest from survival to postoperative outcomes and symptoms. In this systematic review, we investigate gastrointestinal symptoms that occur after a gastrectomy in relation to exocrine pancreatic insufficiency and the effect of pancreatic exocrine enzyme supplementation on these symptoms. METHODS: Online databases PubMed, Embase, and Cochrane Library were systematically searched in accordance with the PRISMA guidelines. Studies that researched gastrointestinal symptoms, exocrine pancreatic function, and enzyme supplementation were identified and assessed. RESULTS: The search resulted in a total of 1,023 articles after exclusion of duplicates. After performing a thorough assessment, 4 studies were included for systematic review. Exocrine pancreatic insufficiency was investigated by 2 studies; the results showed a significant decrease of total exocrine pancreatic function of up to 76%. The other 2 studies investigated the effect of pancreatic enzyme supplementation and found minor improvement in fecal consistency and a decrease in high-degree steatorrhea. No differences in individual symptom scores were reported. CONCLUSION: Gastrointestinal symptoms such as steatorrhea, bloating, and dumping syndrome may be related to exocrine pancreatic function, initiated by total gastrectomy. Treatment with pancreatic enzymes had a minor positive effect on patients. It should be noted that these studies were of a small sample size and low quality. New and larger RCTs are necessary to either prove or disprove the benefit of pancreatic enzyme replacement therapy in the treatment of the gastrointestinal symptoms after total gastrectomy.

A systematic review on the role of imiquimod in lentigo maligna and lentigo maligna melanoma: need for standardization of treatment schedule and outcome measures.

Lentigo maligna (LM) is an in situ variant of melanoma. Our objective was to systematically review clinical and histological clearance and recurrence rates of imiquimod treatment of LM with emphasis on progression to lentigo maligna melanoma (LMM). PubMed, EMBASE and the Cochrane library were searched from inception to May 2015. Articles were included if they described histologically proven LM treated with imiquimod 5% monotherapy or combined with another topical therapy. Analysed outcomes were clinical and histological clearance, recurrence rates and number of LMM. The quality was assessed using the GRADE-like checklist, and results were reported according to the PRISMA Statement. Twenty-six case reports, 11 retrospective studies, three prospective studies and one randomized controlled trial were included. One case report of poor quality was excluded. Complete clinical clearance was seen in 369 of 471 patients (78.3%). Histological clearance was present in 285 of 370 (77%) patients. LMM was diagnosed in nine (1.8%) patients 3.9 months (range 0-11 months) post-treatment. Univariate multinominal logistic regression showed that 6-7 applications/week had a 6.47 greater odds (P = 0.017) of resulting in complete clinical clearance compared to 1-4 applications/week. An intensity of 6-7 applications/week showed a 8.85 greater odds (P = 0.003) of resulting in histological clearance compared to 1-4 applications. Applying imiquimod >60 times during a treatment period of 12 weeks (range 4-36) showed a 7.75 greater odds (P = 0.001) of resulting in histological clearance compared to <60 total applications. In conclusion, a treatment schedule using imiquimod 6-7 applications per week, with at least 60 applications, shows the greatest odds of complete clinical and histological clearance of LM. Imiquimod is an option for patients unfit for or not willing to undergo surgery or radiotherapy. Nine cases of LM progressed to LMM shortly after treatment. Our hypothesis is that these LMM may have been present before starting imiquimod.

A prospective, cohort evaluation of major and minor airway management complications during routine anaesthetic care at an academic medical centre.

The aim of this study was to develop an audit tool to identify prospectively all peri-operative adverse events during airway management in a cost-effective and reproducible way. All patients at VU University Medical Center who required general anaesthesia for elective and emergency surgical procedures were included during a period of 8 weeks. Daily questionnaires and interviews were taken from anaesthesia trainees and anaesthetic department staff members. A total of 2803 patients underwent general anaesthesia, 1384 men and 1419 women, including 2232 elective patients and 571 emergency procedures, 697 paediatric and 2106 adult surgical procedures. A total of 168 airway-related events were reported. The incidence of severe airway management-related events was 24/2803 (0.86%). There were 12 (0.42%) unanticipated ICU admissions, two patients (0.07%) required a surgical airway. There was one (0.04%) death, one cannot intubate cannot oxygenate (0.04%), one aspiration (0.04%) and eight (0.29%) severe desaturations < Sp O2 50%. We suggest that our method to determine and investigate airway management-related adverse events could be adopted by other hospitals.

A systematic review on [(18)F]FLT-PET uptake as a measure of treatment response in cancer patients.

Imaging biomarkers have a potential to depict the hallmarks of cancers that characterise cancer cells as compared to normal cells. One pertinent example is 3'-deoxy-3'-(18)F-fluorothymidine positron emission tomography ([(18)F]FLT-PET), which allows non-invasive in vivo assessment of tumour proliferation. Most importantly, [(18)F]FLT does not seem to be accumulating in inflammatory processes, as seen in [(18)F]-fludeoxyglucose, the most commonly used PET tracer for assessment of cell metabolism. [(18)F]FLT could therefore provide additional information about the tumour biology before, during and after treatment. This systematic review focuses on the use of [(18)F]FLT-PET tumour uptake values as a measure of tumour response to therapeutic interventions. The clinical studies which evaluated the role of [(18)F]FLT-PET as a measure of tumour response to treatment are summarised and the evidence linking [(18)F]FLT-PET tumour uptake values with clinical outcome is evaluated.

Preoperative Methods to Reduce Liver Volume in Bariatric Surgery: a Systematic Review.

BACKGROUND: Patients qualified for gastric bypass surgery have an enlarged and fatty liver. An essential step in gastric bypass surgery is elevation of the left liver lobe to expose the gastroesophageal junction. An enlarged and fatty liver complicates the surgical procedure and increases the risk for laceration of the liver. The aim of our study was to evaluate methods to reduce liver volume in patients prior to gastric bypass surgery. METHODS: A systematic literature search of multiple databases, including PubMed, EMBASE.com, and the Cochrane Library and a hand search of reference lists, was performed. We used the search terms morbid obesity and liver, including their synonyms and controlled terms. Inclusion criteria were as follows: patients with morbid obesity who qualified for bariatric surgery, the use of a preoperative treatment to reduce liver volume, and the use of imaging techniques before and after treatment. RESULTS: In total, 281 patients in 11 different studies were included. Preoperative diets reduced liver size by an average of 14%, alternative methods including nutritional supplements, reduced liver size between 20 and 43%, and an intragastric balloon by 32%. CONCLUSIONS: This review showed that nutritional supplements and intragastric balloon are more effective than low calorie diets in reducing liver volume prior to gastric bypass surgery. However, low calorie diet is the preferable method to reduce liver volume, considering the level of evidence and practical applicability. There is a need for well-designed randomized studies with sufficient power in order to confirm the effectiveness of preoperative methods to reduce liver volume.

Systematic review of patient-reported outcome measures in the surgical treatment of patients with esophageal cancer.

Esophageal cancer is currently the eighth most common cancer worldwide. Improvements in operative techniques and neoadjuvant therapies have led to improved outcomes. Resection of the esophagus carries a high risk of severe complications and has a negative impact on health-related quality of life (QOL). The aim of this study was to assess which patient-reported outcome measures (PROMs) are used to measure QOL after esophagectomy for cancer. A comprehensive search of original articles was conducted investigating QOL after surgery for esophageal carcinoma. Two authors independently selected relevant articles, conducted clinical appraisal, and extracted data (PJ and JS). Out of 5893 articles, 58 studies were included, consisting of 41 prospective and 17 retrospective cohort studies, including a total of 6964 patients. These studies included 11 different PROMs. The existing PROMs could be divided into generic, symptom-specific, and disease-specific questionnaires. The European Organisation for Research and Treatment of Cancer (EORTC) QOL Questionnaire Core 30 (QLQ C-30) along with the EORTC QLQ-OESophagus module OES18 was the most widely used; in 42 and 32 studies, respectively. The EORTC and the Functional Assessment of Cancer Therapy (FACT) questionnaires use an oncological module and an organ-specific module. One validation study was available, which compared the FACT and EORTC, showing moderate to poor correlation between the questionnaires. A great variety of PROMs are being used in the measurement of QOL after surgery for esophageal cancer. A questionnaire with a general module along with a disease-specific module for assessment of QOL of different treatment modalities seem to be the most desirable, such as the EORTC and the FACT with their specific modules (EORTC QLQ-OES18 and FACT-E). Both are developed in different treatment modalities, such as in surgical patients. With regard to reproducibility of current results, the EORTC is recommended.

The influence of prehospital time on trauma patients outcome: a systematic review.

OBJECTIVE: Time is considered an essential determinant in the initial care of trauma patients. Salient tenet of trauma care is the 'golden hour', the immediate time after injury when resuscitation and stabilization are perceived to be most beneficial. Several prehospital strategies exist regarding time and transport of trauma patients. Literature shows little empirical knowledge on the exact influence of prehospital times on trauma patient outcome. The objective of this study was to systematically review the correlation between prehospital time intervals and the outcome of trauma patients. METHODS: A systematic review was performed in MEDLINE, Embase and the Cochrane Library from inception to May 19th, 2014. Studies reporting on prehospital time intervals for emergency medical services (EMS), outcome parameters and potential confounders for trauma patients were included. Two reviewers collected data and assessed the outcomes and risk of bias using the STROBE-tool. The primary outcome was the influence on mortality. RESULTS: Twenty level III-evidence articles were considered eligible for this systematic review. Results demonstrate a decrease in odds of mortality for the undifferentiated trauma patient when response-time or transfer-time are shorter. On the contrary increased on-scene time and total prehospital time are associated with increased odds of survival for this population. Nevertheless rapid transport does seem beneficial for patients suffering penetrating trauma, in particular hypotensive penetratingly injured patients and patients with a traumatic brain injury. CONCLUSION: Swift transport is beneficial for patients suffering neurotrauma and the haemodynamically unstable penetratingly injured patient. For haemodynamically stable undifferentiated trauma patients, increased on-scene-time and total prehospital time does not increase odds of mortality. For undifferentiated trauma patients, focus should be on the type of care delivered prehospital and not on rapid transport.

Complications of mandibular distraction osteogenesis for congenital deformities: a systematic review of the literature and proposal of a new classification for complications.

A systematic review of English and non-English language articles on the complications of mandibular distraction osteogenesis (MDO) for patients with congenital deformities was performed, in accordance with the PRISMA statement. Search terms expressing distraction osteogenesis were used in 'AND' combination with search terms comprising 'mandible' and terms for complication, failure, and morbidity. A search using PubMed (National Library of Medicine, NCBI), EMBASE, and the Cochrane Central Register of Controlled Trials yielded 644 articles published between 1966 and mid October 2013. Clinical articles that reported complications related to MDO were included. Finally 81 articles on MDO in congenital deformities were eligible and were screened in detail. Complications including minor infection (6.0%), device-related problems (7.3%), skeletal open bite (2.4%), hypertrophic scar formation (2.1%), facial nerve palsy (1.8%), neurosensory disturbances of the inferior alveolar nerve (1.9%), and (fibrous) non-union (0.7%) were seen. A new index for more detailed classification of complications in MDO is proposed based on six categories that indicate the impact of the complication and its further treatment or final results. The proposed complication index may be a useful tool to classify complications related to MDO.

Complications of mandibular distraction osteogenesis for developmental deformities: a systematic review of the literature.

A systematic review of English and non-English articles on the complications of mandibular distraction osteogenesis (MDO) for patients with developmental deformities was performed, in accordance with the PRISMA statement. Search terms expressing distraction osteogenesis were used in 'AND' combination with search terms comprising 'mandible' and terms for complication, failure, and morbidity. A search using PubMed (National Library of Medicine, NCBI), EMBASE, and Cochrane Controlled Trials Register yielded 644 articles published between 1966 and mid October 2013. Clinical articles that reported complications related to MDO in developmental deformities were included. Two hundred and fifty articles were eligible and were screened in detail. A total of 32 articles reporting the cases of 565 patients were finally included. Patients underwent mandibular lengthening and transverse widening. A total of 211 complications were reported (37.4%); these were classified according to an index that indicates the clinical impact. Inferior alveolar nerve (IAN) neurosensory disturbances, minor infection, device failure, anterior open bite, permanent dental damage, and skeletal relapse were most represented. Complications that resolved spontaneously (type I) were seen in 11.0%, medically or technically manageable complications, without hospitalization, were seen in 10.8% (type II), and permanent complications (type VI) were seen in 9.6%.

The impact of the use of the Early Warning Score (EWS) on patient outcomes: a systematic review.

BACKGROUND: Acute deterioration in critical ill patients is often preceded by changes in physiological parameters, such as pulse, blood pressure, temperature and respiratory rate. If these changes in the patient's vital parameters are recognized early, excess mortality and serious adverse events (SAEs) such as cardiac arrest may be prevented. The Early Warning Score (EWS) is a scoring system which assists with the detection of physiological changes and may help identify patients at risk of further deterioration. OBJECTIVES: The aim of this systematic review is to evaluate the impact of the use of the Early Warning Score (EWS) on particular patient outcomes, such as in-hospital mortality, patterns of intensive care unit admission and usage, length of hospital stay, cardiac arrests and other serious adverse events of adult patients on general wards and in medical admission units. DESIGN AND SETTING: Systematic review of studies identified from the bibliographic databases of PubMed, EMBASE.com and The Cochrane Library. SELECTION CRITERIA: All controlled studies which measured in-hospital mortality, ICU mortality, serious adverse events (SAEs), cardiopulmonary arrest, length of stay and documentation of physiological parameters which used a EWS on the ward or the emergency department to identify patients at risk were included in the review. DATA COLLECTION AND ANALYSIS: Three reviewers (NA, AT and EH) independently screened all potentially relevant titles and abstracts for eligibility, by using a standardized data-worksheet. Meta-analysis was not possible due to heterogeneity. MAIN RESULTS: Seven studies met the inclusion criteria. The results of our included studies were mixed, with a positive trend towards better clinical outcomes following the introduction of the EWS chart, sometimes coupled with an outreach service. Six of the seven included studies used mortality as an endpoint: two of these studies reported no significant difference in in-hospital mortality rate; two found a significant reduction of in-hospital mortality; two other studies described a trend towards improved survival. Although, both ICU mortality and serious adverse events were not significantly improved, there was a trend towards reduction of these endpoints after introduction of the EWS. However only two studies looked respectively at each endpoint. There were conflicting results concerning cardiopulmonary arrests. One study found a reduction in the incidence of cardiac arrest calls as well as in the mortality of patients who underwent CPR, while another one found an increased incidence of cardio-pulmonary arrests. Neither study met all methodological quality criteria. CONCLUSION: The EWS itself is a simple and easy to use tool at the bedside, which may be of help in recognizing patients with potential for acute deterioration. Coupled with an outreach service, it may be used to timely initiate adequate treatment upon recognition, which may influence the clinical outcomes positively. However, the use of adapted forms of the EWS together with different thresholds, poor or inadequate methodology makes it difficult in drawing comparisons. A general conclusion can thus not be generated from the lack of use of a single standardized score and the use of different populations. In future large multi-centre trials using one standardized score are needed also in order to facilitate comparison.

Slipped capital femoral epiphysis and its association with endocrine, metabolic and chronic diseases: a systematic review of the literature.

PURPOSE: Puberty, obesity, endocrine and chronic systemic diseases are known to be associated with slipped capital femoral epiphysis (SCFE). The mechanical insufficiency of the physis in SCFE is thought to be the result of an abnormal weakening of the physis. However, the mechanism at the cellular level has not been unravelled up to now. METHODS: To understand the pathophysiology of endocrine and metabolic factors acting on the physis, we performed a systematic review focussing on published studies reporting on hormonal, morphological and cellular abnormalities of the physis in children with SCFE. In addition, we looked for studies of the effects of endocrinopathies on the human physis which can lead to cause SCFE and focussed in detail on hormonal signalling, hormone receptor expression and extracellular matrix (ECM) composition of the physis. We searched in the PubMed, EMBASE.com and The Cochrane Library (via Wiley) databases from inception to 11th September 2012. The search generated a total of 689 references: 382 in PubMed, 232 in EMBASE.com and 75 in The Cochrane Library. After removing duplicate papers, 525 papers remained. Of these, 119 were selected based on titles and abstracts. After excluding 63 papers not related to the human physis, 56 papers were included in this review. RESULTS: Activation of the gonadal axis and the subsequent augmentation of the activity of the growth hormone-insulin-like growth factor 1 (GH-IGF-1) axis are important for the pubertal growth spurt, as well as for cessation of the physis at the end of puberty. The effects of leptin, thyroid hormone and corticosteroids on linear growth and on the physis are also discussed. Children with chronic diseases suffer from inflammation, acidosis and malnutrition. These consequences of chronic diseases affect the GH-IGF-1 axis, thereby, increasing the risk of the development of SCFE. The risk of SCFE and avascular necrosis in children with chronic renal insufficiency, growth hormone treatment and renal osteodystrophy remains equivocal. CONCLUSIONS: SCFE is most likely the result of a multi-factorial event during adolescence when height and weight increase dramatically and the delicate balance between the various hormonal equilibria can be disturbed. Up to now, there are no screening or diagnostic tests available to predict patients at risk.