Prediction of osteoporotic fragility re-fracture with lumbar spine DXA-based derived bone strain index: a multicenter validation study.

A new qualitative index of bone strength, based on finite element analysis and named bone strain index, has been recently developed from lumbar DXA scan. This study shows that BSI predicts subsequent re-fracture in osteoporotic patients affected by fragility fractures. INTRODUCTION: Dual-energy X-ray absorptiometry (DXA) can provide quantitative (bone mineral density, BMD) and qualitative (trabecular bone score, TBS) indexes of bone status, able to predict fragility fractures in most osteoporotic patients. A new qualitative index of bone strength, based on finite element analysis and named bone strain index (BSI), has been recently developed from lumbar DXA scan. This study presents the validation results of BSI prediction for re-fracture in osteoporotic patients with fragility fractures. METHODS: In three academic hospitals, 234 consecutive fractured patients with primary osteoporosis (209 females) performed a spine X-ray for the calculation of spine deformity index (SDI) and DXA densitometry for BMD, TBS and BSI at the basal time and in the follow-up at each clinical check. A subsequent fracture was considered as one unity increase of SDI. RESULTS: For each unit increase of the investigated indexes, the univariate hazard ratio of re-fracture, 95% CI, p value and proportionality test p value are for age 1.040, 1.017-1.064, 0.0007 and 0.2529, respectively, and for BSI 1.372, 1.038-1.813, 0.0261 and 0.5179, respectively. BSI remained in the final multivariate model as a statistically significant independent predictor of a subsequent re-fracture (1.332, 1.013-1.752 and 0.0399) together with age (1.039, 1.016-1.064 and 0.0009); for this multivariate model proportionality test, p value is 0.4604. CONCLUSIONS: BSI appears to be a valid DXA index of prediction of re-fracture, and it can be used for a more refined risk assessment of osteoporotic patients.

Skeletal involvement in type 1 Gaucher disease: Not just bone mineral density.

Gaucher disease is characterized by multi-organ infiltration of phospholipid-laden macrophages. Bone involvement is characterized by typical deformities, osteopenia/osteoporosis, pathological fractures, and bone marrow infiltration (avascular osteonecrosis, infarction). Estimation of skeletal disease includes bone quality that contributes substantially to bone strength. We studied 23 type 1 Gaucher patients (median age 22years, range 3-73) on Enzyme Replacement Therapy from 2months to 26years (median 7years); 4 patients had pathological fractures, 10 bone infarctions, 6 avascular osteonecrosis. We noninvasively assessed bone quality by trabecular microarchitecture and macroscopic geometry, using two innovative dual-energy X-ray absorptiometry tools: Trabecular Bone Score (TBS) and Hip Structural Analysis (HSA). Bone quality parameters distinguished the patients with skeletal complications. TBS was significantly lower in patients with avascular osteonecrosis (p=0.049) and pathological fractures (p=0.024), while it could not identify those with bone infarctions. Among HSA parameters, the Cross Sectional Area of the intertrochanteric region and the Buckling Ratio of the narrow neck allowed the distinction of patients with avascular osteonecrosis. BMD was low in 11 patients (50%); neither BMD nor HSA were associated with pathological fractures. The combined evaluation of bone quality and bone quantity is useful to identify GD patients with more severe skeletal involvement.

Managing chronic myeloid leukaemia in the elderly with intermittent imatinib treatment.

The aim of this study was to investigate the effects of a non-standard, intermittent imatinib treatment in elderly patients with Philadelphia-positive chronic myeloid leukaemia and to answer the question on which dose should be used once a stable optimal response has been achieved. Seventy-six patients aged ⩾65 years in optimal and stable response with ⩾2 years of standard imatinib treatment were enrolled in a study testing a regimen of intermittent imatinib (INTERIM; 1-month on and 1-month off). With a minimum follow-up of 6 years, 16/76 patients (21%) have lost complete cytogenetic response (CCyR) and major molecular response (MMR), and 16 patients (21%) have lost MMR only. All these patients were given imatinib again, the same dose, on the standard schedule and achieved again CCyR and MMR or an even deeper molecular response. The probability of remaining on INTERIM at 6 years was 48% (95% confidence interval 35-59%). Nine patients died in remission. No progressions were recorded. Side effects of continuous treatment were reduced by 50%. In optimal and stable responders, a policy of intermittent imatinib treatment is feasible, is successful in about 50% of patients and is safe, as all the patients who relapsed could be brought back to optimal response.

Symptom-association probability between meal ingestion and abdominal pain in patients with irritable bowel syndrome. Does somatization play a role?

BACKGROUND: Patients with irritable bowel syndrome (IBS) complain of postprandial abdominal pain, but it is still unknown how much of this association is due to chance. Somatization enhances the perception of symptoms after a meal. We assessed: (i) the proportion of meal-related pain periods and the symptom-association probability (SAP) between the two variables in IBS patients; and (ii) how this association is affected by somatization. METHODS: Seventy IBS patients recorded the times of meals and abdominal pain in a 10-day diary card. The proportion of postmeal pain periods was calculated in relation to the total number of 90-min periods with pain. Fisher's exact test was used to calculate the probability (p) of an association within a time window of 90 min, and the SAP was calculated as (1 - p) × 100%. The IBS Symptom Severity Scale, the SCL90-R for psychological symptoms, and the SF-36 for the quality of life were completed. KEY RESULTS: The proportion of postmeal pain periods was 42 ± 27%. SAP was significant (p < 0.05) in 32 patients (45%). Somatization was altered in 30 patients (47%), who were younger and had more severe IBS and a poorer quality of life. Somatization did not influence the association between meal ingestion and abdominal pain. CONCLUSIONS & INFERENCES: Meal ingestion and abdominal pain are significantly associated in 45% of IBS patients. Somatization influences IBS severity and the patients' quality of life, but not the strength of the association between eating and pain.

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.

Buprenorphine versus tramadol as perineural adjuvants for postoperative analgesia in patients undergoing arthroscopic rotator cuff repair under middle interscalene block: a retrospective study.

BACKGROUND: The aim of this retrospective study was to compare buprenorphine and tramadol, in order to assess their different efficacy in prolonging postoperative analgesia and their associated side effects when used as perineural adjuvants with a local anesthetic. METHODS: The clinical records of 161 consecutive ASA 1-2 adult patients scheduled for arthroscopic rotator cuff repair and fulfilling the inclusion/exclusion criteria were reviewed retrospectively. The anaesthesia was performed using the middle interscalene block (MIB). The 161 patients were divided into three groups (A, B, T) according to their utilization of buprenorphine (B), tramadol (T) or neither of the latter (A) as perineural adjuvants: group A (54 patients) - levobupivacaine 0.75%, 0.4 mL/kg; group B (56 patients) - levobupivacaine 0.75%, 0.4 mL/kg + 0.15 mg buprenorphine; group T (51 patients) - levobupivacaine 0.75%, 0.4 mL/kg + 100 mg tramadol. RESULTS: The results showed that the group treated with buprenorphine benefited from a longer post-operative analgesia than that treated with local anesthetic alone (P<0.0001). Otherwise, a less evident not statistically significant (P=0.4825) difference turned out between the group treated with the anesthetic alone and the group treated with tramadol as adjuvant. No difference turned out to be between the local anesthetic alone treatment and the tramadol-local anesthetic one (P=0.4825; HR=0.863, 95% CI 0.574-1.299); on the contrary, a significant difference was demonstrated between the buprenophine-local anesthetic group and the local anesthetic alone one (P<0.0001; HR=0.330, 95% CI 0.216-0.530) CONCLUSION: Both buprenorphine and tramadol are effective as perineural adjuvants used in order to prolong the postoperative analgesia, buprenorphine proving more efficacious for this purpose than tramadol.

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.

Is the subjective perception of lactose intolerance influenced by the psychological profile?

BACKGROUND: Symptoms of lactose intolerance are often attributed to lactose malabsorption but, as this relationship has not been demonstrated when a small dose of lactose similar to that contained in one cup of milk is ingested by intolerant patients, psychological factors may play a role in altered symptom perception. AIM: To assess the hypothesis that the psychological profile influences the symptoms of lactose intolerance. METHODS: One hundred and two consecutive patients underwent a 15 g lactose hydrogen breath test to assess lactose malabsorption. The patients recorded the presence and severity of symptoms of lactose intolerance during the breath test using visual analogue scales. The psychological profile was assessed using a psychological symptom checklist, and health-related quality of life by means of the short-form health survey. RESULTS: Lactose malabsorption and intolerance were diagnosed in, respectively, 18% and 29% of the patients. The two conditions were not associated, and the severity of intolerance was even less in the patients with malabsorption. Multivariate logistic analysis showed that a high somatisation t-score was significantly associated with lactose intolerance (odds ratio 4.184; 1.704-10.309); the effects of the other psychological variables and of lactose malabsorption were not statistically significant. Health-related quality of life was significantly reduced in the patients with somatisation, but not in those with lactose malabsorption. CONCLUSIONS: The symptoms of lactose intolerance during hydrogen breath testing at a low physiological lactose load, are unrelated to lactose malabsorption, but may reveal a tendency towards somatisation that could impair the quality of life.

Serosurvey against H5 and H7 avian influenza viruses in Italian poultry workers.

Highly pathogenic (HP) and low pathogenic (LP) avian influenza viruses (AIVs) belonging to H5 and H7 subtypes have been found to be associated with human infection as the result of direct transmission from infected poultry. Human infections by AIVs can cause mild or subclinical disease, and serosurveys are believed to represent an important tool to identify risk of zoonotic transmission. Therefore, we sought to examine Italian poultry workers exposed during LPAI and HPAI outbreaks with the aim of assessing serologic evidence of infection with H5 and H7 AIVs. From December 2008 to June 2010 serum samples were collected from 188 poultry workers and 379 nonexposed controls in Northern Italy. The hemagglutination inhibition (HI) assay using horse red blood cells (RBCs) and a microneutralization (MN)-enzyme-linked immunosorbent assay test were used to analyze human sera for antibodies against the following H5 and H7 LPAI viruses: A/Dk/It/4445/07(H5N2); A/Ty/It/2369/09(H5N7); A/Ty/It/218-193/ 10; A/Ck/It/3775/99(H7N1); A/Ty/It/214845/03(H7N3); and A/Dk/It/332145/09(H7N3). Since previous studies identified low antibody titer to AIVs in people exposed to infected poultry, a cutoff titer of > or = 1:10 was chosen for both serologic assays. Only HI-positive results confirmed by MN assay were considered positive for presence of specific antibodies. The Fisher exact test was used to analyze differences in seroprevalence between poultry workers and control groups, with the significance level set at P < 0.05. MN results showed a proportion of H7-seropositive poultry workers (6/188, i.e., 3.2%), significantly higher than that of controls (0/379), whereas no MN-positive result was obtained against three H5 LPAI subtypes recently identified in Italy. In conclusion, the survey indicated that assessing seroprevalence can be an important tool in risk assessment and health,surveillance of poultry workers.

Psychopathologic, neuropsychological and functional outcome measures during cognitive rehabilitation in schizophrenia: a prospective controlled study in a real-world setting.

BACKGROUND: Cognitive dysfunction has been demonstrated in patients with schizophrenia, and this may affect patients' functional outcome. The improvement of such dysfunction by means of cognitive remediation interventions has become a relevant target in the care of schizophrenia. OBJECTIVE: To assess the effectiveness of the cognitive subprograms of Integrated Psychological Therapy (IPT) on symptomatological, neuropsychological and functional outcome variables and to analyze the relationships between cognitive and functional outcome changes in schizophrenia. METHODS: Thirty-two patients with schizophrenia were assigned to cognitive remediation (IPT-cog) or usual rehabilitative interventions in a naturalistic setting of care. Clinical, neuropsychological and functional outcome variables were assessed at baseline and after 24 weeks of treatment. RESULTS: The IPT-cog group improved significantly more than the comparison group with respect to psychopathological and functional outcome variables. Moreover, only the IPT-cog group improved significantly in the neuropsychological domains of verbal and working memory, with specific significant correlations between neurocognitive performance and functional outcome changes. CONCLUSIONS: The results of the study confirm the effectiveness of the cognitive remediation component of IPT in schizophrenia, and indicate that some of the changes in functional outcome may be mediated by improvement in specific cognitive domains.

Positive end-expiratory pressure, prone positioning, and activated protein C: a critical review of meta-analyses.

The results of meta-analyses on the effectiveness of high positive end-expiratory pressure (PEEP) and prone positioning in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) are not consistent. In addition, the meta-analyses on the activated protein C in patients with sepsis combine trials with discordant results. Therefore, the aim of this paper was to give a critical review of these meta-analyses. All relevant meta-analyses were identified by a computerized search of PubMed using combinations of the following terms: acute lung injury, acute respiratory distress syndrome, positive end-expiratory pressure, mechanical ventilation, prone position, drotrecogin, activated protein C, sepsis, and septic patients. A high level of PEEP and prone ventilation was shown to reduce the mortality in patients with severe acute hypoxemic respiratory failure. Although the evidence for the efficacy of activated protein C is not conclusive, it should be considered in patients that are at a high risk for death without any contraindications related to bleeding risk. Meta-analysis models can be very useful for clinical decisions if they include all of the similar papers on a medical topic and are correct from the methodological point of view; however, these results must be checked by a careful and well-informed reader.

Complete recovery of intestinal mucosa occurs very rarely in adult coeliac patients despite adherence to gluten-free diet.

BACKGROUND: Expected benefits of gluten-free diet (GFD) in coeliac patients include healing of small intestinal mucosa, but it remains unclear to what extent this benefit is achieved in adults. AIM: To assess factors affecting histological outcome of GFD in a large cohort of adult coeliac patients. METHODS: We extracted information on 465 consecutive coeliac patients studied before and during GFD. RESULTS: Duodenal biopsies at diagnosis were classified as Marsh I in 11, II in 25 and III in 429 cases. After a median 16 months GFD, 38 (8%) patients had histological 'normalization', 300 (65%) had 'remission' with persistent intraepithelial lymphocytosis, 121(26%) had 'no change' and 6 (1%) had 'deterioration'. Coeliac disease related serology was negative in 83% of patients with Marsh III lesion during GFD. Male gender and adherence to GFD were independently associated with histological 'normalization' and 'remission'. Persistence of intraepithelial lymphocytosis was not associated with human lymphocyte antigen gene dose or with Helicobacter pylori infection. CONCLUSIONS: Complete normalization of duodenal lesions is exceptionally rare in adult coeliac patients despite adherence to GFD, symptoms disappearance and negative CD related serology. Control biopsies are mandatory to identify lack of response to gluten-free diet.

Elevation of serum gamma-glutamyltranspeptidase activity is frequent in chronic hepatitis C, and is associated with insulin resistance.

BACKGROUND AND AIMS: Serum gamma-glutamyltranspeptidase level is often increased in patients with chronic hepatitis C, and we aimed to identify factors associated with this phenomenon in patients completely abstinent from alcohol (teetotaller). PATIENTS AND METHODS: 71 teetotaller patients have been identified by personal history, questioning of relatives, CAGE questionnaire administration and unscheduled alcoholemia measurements. RESULTS: 39 patients (55%) had elevated (>50IU/L) gamma-glutamyltranspeptidase level. Body mass index, insulin and C-peptide level, insulin resistance, piecemeal necrosis score > or =3, fibrosis score > or =2 and steatosis score > or =1 were significantly higher in these patients than in those (n=32) with normal gamma-glutamyltranspeptidase. At multiple linear regression analysis gamma-glutamyltranspeptidase level was associated with C-peptide level, insulin resistance and histopathologic grading. At multiple logistic regression analysis, C-peptide level (OR=2.13) and piecemeal necrosis score > or =3 (OR=4.59) were the only factors independently associated with elevated gamma-glutamyltranspeptidase. Sustained virological response during pegylated interferon plus ribavirine treatment was achieved by 97% and 49% patients with normal and elevated gamma-glutamyltranspeptidase, respectively (p=0.0001). CONCLUSION: Serum gamma-glutamyltranspeptidase level is often elevated in chronic hepatitis C and is associated with metabolic and inflammatory factors; this phenomenon may contribute to explain and to predict resistance to treatment in this subgroup of patients.

Statistical methods for evidence-based medicine: the diagnostic test. Part II.

Part II of this work addresses the use of likelihood ratios for the calculation of a positive predictive value (PPV) and a negative predictive value (NPV) for patient diagnosis. These two values are the most useful indices in the application of a diagnostic test in order to make a diagnosis for a patient. Furthermore, the relevance of sample size is also addressed by providing background theory and pertinent tables. These basic topics for assessing the validity of a diagnostic test and for performing appropriate and valid case vs control studies are explained in a simple way for a clinical audience with a working example.

Statistical methods for evidence-based medicine: the diagnostic test. Part I.

According to evidence-based medicine (EBM), physicians must be able to assess and understand scientific evidence generated from biomedical research. Among the many statistical methods involved in the proof of the evidence, an essential area concerns how to select and interpret diagnostic tests to confirm or exclude a diagnosis. Rather surprisingly, these statistical methods are not always correctly reported or satisfactorily explained in some EBM reference books, which leads to misunderstandings and incorrect analyses of published studies in the biomedical literature. In this paper, the authors consider the methodology for performing diagnostic test studies and a correct analysis of the diagnostic test results by explaining it for a clinical audience with a working example.

Coeliac disease: a histological follow-up study.

AIMS: To assess the histological response to a gluten-free diet (GFD) in a series of coeliac patients in clinical remission, of different ages and with varying degrees of mucosal damage at diagnosis. METHODS AND RESULTS: Biopsy samples from 249 coeliac patients (F 165, M 84) were analysed basally and after clinical and biochemical remission following a GFD. All patients showed an improvement in mucosal findings after starting a GFD, but complete histological normalization was observed in 74.1% of paediatric cases (diagnosed before 14 years of age) and in only 17.5% of adults. Statistical analysis showed that sex, the clinical picture at diagnosis and the length of time between biopsy at the time of diagnosis and on a GFD were not related to histological normalization. In contrast, the age at diagnosis was statistically significantly related to it (P < 0.0001). In addition, the presence/absence of Helicobacter pylori was independent of the normalization of the duodenal mucosa. CONCLUSIONS: In clinical practice the criteria for diagnosis of coeliac disease are sufficiently standardized, whereas for follow-up they are less well defined. We suggest that in order to compare the results from different studies, it should be stated whether remission after treatment is based on clinical or histological criteria or both.