Wilson disease: copper deficiency and iatrogenic neurological complications with zinc therapy.

A 17-year-old female was diagnosed with Wilson disease and commenced on oral zinc therapy. She re-presented 6 months later with a fall and had classical signs of subacute combined degeneration of the spinal cord confirmed on nerve conduction studies, as a result of zinc-induced copper deficiency. After 6 months of copper therapy, she made a complete recovery with no residual neurological deficits. Early detection of zinc-induced copper deficiency and stringent follow-up mechanisms are crucial. Early initiation of copper replacement may both limit and completely reverse neurological deficits.

Effect of Intravenous Fluids and Analgesia on Dysmotility in Patients With Acute Pancreatitis: A Prospective Cohort Study.

OBJECTIVES: Analgesia and intravenous fluid resuscitation are cornerstones of initial patient management in acute pancreatitis (AP). The aim was to investigate the effect of intravenous fluids and analgesia on gastrointestinal motility in the early course of AP. METHODS: Gastrointestinal dysmotility was assessed using the Gastroparesis Cardinal Symptom Index (GCSI). One-way analysis of variance and analysis of covariance were conducted, adjusting for age, sex, body mass index, severity of AP, preexisting diabetes mellitus, and time from first symptom onset to hospital admission. RESULTS: A total of 108 patients with AP were prospectively enrolled. Opioid analgesia, when compared with nonopioid analgesia, was significantly associated with increase in total GCSI score in both unadjusted and adjusted analyses. There was no significant difference between aggressive and nonaggressive fluid resuscitation in both unadjusted and adjusted analyses. A combination of opioids and any intravenous fluids was associated with a significantly increased total GCSI score compared with opioids and no intravenous fluids in both unadjusted and adjusted analyses. Duration of symptoms was the confounder that significantly affected 6 of 9 studied associations. CONCLUSIONS: Intravenous fluids and analgesia significantly affect motility independent of severity and other covariates. Guidelines on prudent use of opioids and fluids in AP need to be developed, particularly taking into account duration of symptoms from onset to hospitalization.

The effect of Rapid Response System revision on standard and specific intensive care unit outcomes in a regional hospital.

Hospital systems for the recognition (afferent limb) and management (efferent limb) of deteriorating patients, or Rapid Response Systems (RRSs), are being mandated worldwide, in spite of conflicting evidence regarding their efficacy. We have evaluated the impact of an Adult Deterioration Detection System (Q-ADDS)-based RRS specifically on illness severity at intensive care unit (ICU) admission and ICU length of stay (LOS), as well as previously studied endpoints. We undertook a retrospective, single-centre observational study comparing equivalent 18-month periods before the Q-ADDS-based RRS, and after implementation. The primary endpoints of the study were illness severity of unplanned ICU admissions from the ward, ICU length of stay, and ICU mortality. Secondary endpoints were RRS call numbers, rate of unplanned ICU admissions, and ward-based cardiorespiratory arrests. Following the introduction of the new RRS, Acute Pain and Chronic Health Evaluation (APACHE) II (17 versus 21, P <0.001), APACHE III (64 versus 68, P=0.011) and Simplified Acute Physiology Score (35 versus 38, P=0.044) scores at ICU admission from the ward were reduced. Fewer patients were in the >50% predicted mortality range of APACHE II (16% versus 32%, P <0.001), APACHE III (18% versus 28%, P=0.012) and Simplified Acute Physiology Score (14% versus 24%, P=0.006). ICU mortality was unchanged (13.7% versus 13.8%, P=0.93). ICU LOS was reduced (3 versus 4 days, P=0.02); prolonged stay (>7 days) was not significantly changed (19% versus 27%, P=0.055). Unplanned ICU admissions, cardiorespiratory arrests and hospital mortality were unchanged. The frequency of RRS activation (48 versus 11 per 1,000 admissions, P <0.001) was markedly increased. This Q-ADDS form-based RRS has resulted in lower illness severity at ICU admission from the ward, and fewer patients with scores associated with a >50% predicted mortality. Overall, ICU length of stay was reduced. These specific outcomes may reliably reflect RRS efficacy, even in smaller centres.

Ectopic fat accumulation in the pancreas and its clinical relevance: A systematic review, meta-analysis, and meta-regression.

OBJECTIVE: Growing evidence suggests that individuals with excessive fat in the pancreas are at an increased risk of chronic metabolic disorders. The aim was to systematically review studies on non-alcoholic fatty pancreas disease (NAFPD) with a view to determine its prevalence, associations with metabolic co-morbidities, and to suggest normal pancreatic fat percentage threshold. METHODS: Three electronic databases (MEDLINE, Scopus, and Embase) were queried. Studies in humans were eligible for inclusion if they provided data on NAFPD and/or pancreatic fat percentage. Where possible, data were pooled using random-effects meta-analysis and the effect of covariates analysed using meta-regression. RESULTS: Pooling data on pancreatic fat percentage from nine studies (1209 healthy individuals who underwent magnetic resonance imaging), yielded the weighted mean and weighted standard deviation of 4.48% and 0.87%, respectively. Pooling data on NAFPD from eleven studies (12,675 individuals), yielded the pooled prevalence of 33% (95% confidence interval, 24% - 41%). Meta-regression analysis showed that the prevalence of NAFPD was independent of age and sex. The presence of NAFPD was associated with a significantly increased risk of arterial hypertension (risk ratio 1.67; 95% confidence interval, 1.32-2.10; p<0.0001), diabetes mellitus (risk ratio 2.08; 95% confidence interval, 1.44-3.00; p=0.0001), and metabolic syndrome (risk ratio 2.37; 95% confidence interval, 2.07-2.71; p<0.0001). CONCLUSION: The findings indicate that NAFPD is a frequent clinical entity, associated with significantly increased risk of metabolic syndrome and its components. The normal pancreatic fat cut-off point of 6.2% may be recommended for use in future prospective studies.

Incidence and predictors of oral feeding intolerance in acute pancreatitis: A systematic review, meta-analysis, and meta-regression.

BACKGROUND: Tolerance of oral food is an important criterion for hospital discharge in patients with acute pancreatitis. Patients who develop oral feeding intolerance have prolonged hospitalisation, use additional healthcare resources, and have impaired quality of life. This study aimed to quantify the incidence of oral feeding intolerance, the effect of confounders, and determine the best predictors of oral feeding intolerance. METHODS: Clinical studies indexed in three electronic databases (EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials) were reviewed. Incidence and predictor data were meta-analysed and possible confounders were investigated by meta-regression analysis. RESULTS: A total of 22 studies with 2024 patients met the inclusion criteria, 17 of which (with 1550 patients) were suitable for meta-analysis. The incidence of oral feeding intolerance was 16.3%, and was not affected by WHO region, age, sex, or aetiology of acute pancreatitis. Nine of the 22 studies investigated a total of 62 different predictors of oral feeding intolerance. Serum lipase level prior to refeeding, pleural effusions, (peri)pancreatic collections, Ranson score, and Balthazar score were found to be statistically significant in meta-analyses. CONCLUSIONS: Oral feeding intolerance affects approximately 1 in 6 patients with acute pancreatitis. Serum lipase levels of more than 2.5 times the upper limit of normal prior to refeeding is a potentially useful threshold to identify patients at high risk of developing oral feeding intolerance.

Ghrelin and gastroparesis as early predictors of clinical outcomes in acute pancreatitis.

BACKGROUND: Impaired motor and hormonal gastrointestinal functions have been implicated in the pathogenesis of acute pancreatitis. The aim of the present study was to investigate the predictive value of the Gastroparesis Cardinal Symptom Index and serum ghrelin in the development of clinically meaningful outcomes in patients with acute pancreatitis. METHODS: This was a prospective clinical study. The Gastroparesis Cardinal Symptom Index and serum ghrelin were measured for 48 h after hospitalization. Univariate and multivariate logistic regression analyses were conducted. RESULTS: The Gastroparesis Cardinal Symptom Index total score alone on day 2 was a significant predictor of oral feeding intolerance in both unadjusted (odds ratio 1.21 (1.01-1.46), P = 0.04) and adjusted (odds ratio 1.30 (1.01-1.69), P = 0.05) analyses. Adding ghrelin to Gastroparesis Cardinal Symptom Index further improved prediction in both unadjusted (odds ratio 1.26 (1.02-1.56), P = 0.03) and adjusted (odds ratio 1.53 (1.00-2.35), P = 0.05) analyses. CONCLUSION: This pilot study demonstrates that the Gastroparesis Cardinal Symptom Index has a potential to be used as a predictor of oral feeding intolerance. Ghrelin, when combined with the Gastroparesis Cardinal Symptom Index, may further improve the predictive accuracy. These findings need to be confirmed in larger studies.

Global incidence and mortality of pancreatic diseases: a systematic review, meta-analysis, and meta-regression of population-based cohort studies.

BACKGROUND: There is a lack of robust estimates of the worldwide incidence and mortality of acute pancreatitis, chronic pancreatitis, pancreatic cysts, and pancreatic cancer in the general population. Our aim was to quantitate and compare the incidence and mortality of major pancreatic diseases in high-quality population-based cohort studies. METHODS: Three databases (PubMed, Embase, and Scopus) were searched independently by two reviewers. Data from eligible studies were subject to meta-analysis to obtain global estimates. A number of prespecified subgroup analyses and meta-regression analyses were also done. FINDINGS: 48 population-based cohort studies (35 on pancreatic cancer, ten on acute pancreatitis, three on chronic pancreatitis, and none on pancreatic cysts) were identified, with a total study population of 296 million individuals and 119 000 patients with pancreatic diseases. Global estimates of incidence and mortality were 8·14 cases (95% CI 6·63-9·98) per 100 000 person-years and 6·92 deaths (95% CI 3·72-12·89) per 100 000 person-years for pancreatic cancer, 33·74 cases (95% CI 23·33-48·81) per 100 000 person-years and 1·60 deaths (95% CI 0·85-1·58) per 100 000 person-years for acute pancreatitis, and 9·62 cases (95% CI 7·86-11·78) per 100 000 person-years and 0·09 deaths (95% CI 0·02-0·47) per 100 000 person-years for chronic pancreatitis. Subgroup analysis based on the WHO regions showed that the incidences of both pancreatic cancer and acute pancreatitis, and mortality from pancreatic cancer, were significantly higher in the American region than in the European and Western Pacific regions, while the incidence of chronic pancreatitis was significantly higher in the European region than in the American region. Mortality from pancreatic cancer was lowest in the Southeast Asian region. The incidence of chronic pancreatitis was twice as high in men as in women, although there was no difference between sexes for pancreatic cancer or acute pancreatitis. INTERPRETATION: Globally, acute pancreatitis is the most common pancreatic disease whilst pancreatic cancer is the most lethal. However, their burden is not equal across the globe. The epidemiological estimates reported in this study could inform future high-quality studies. FUNDING: None.

Association between oral feeding intolerance and quality of life in acute pancreatitis: A prospective cohort study.

OBJECTIVE: Oral feeding intolerance (OFI) is a common complication of nutritional management in acute pancreatitis (AP) and is associated with significantly worse clinical outcomes and increased cost of treatment. However, changes in patient-reported outcomes associated with OFI during AP and effect of OFI on quality of life (QoL) have, to our knowledge, never been studied. The aim of this study was to investigate the relationship between OFI and QoL in patients with AP. METHODS: We conducted a prospective cohort study of patients with AP. Patients were grouped according to whether they developed OFI during hospitalization. QoL was recorded daily during hospitalization and at 1 and 4 wk after discharge. One-way analysis of covariance and repeated measures analysis were conducted. P < 0.05 was accepted as statistically significant. RESULTS: The study included 131 patients with AP. Fifty-two (40%) developed OFI during hospitalization. Overall QoL was significantly impaired in the OFI group (mean difference = -16.1; 95% confidence interval, -24.4 to -7.8; P ≤ 0.001). Five individual domains-physical limitations, psychological function, sleep, pain, and visceral function-were significantly impaired in the OFI group during hospitalization. Overall QoL improved significantly within each group from hospitalization to follow-up (P < 0.001) with no significant difference between the two groups at follow-up (mean difference = -2; 95% confidence interval, -7.1 to 3.2; P = 0.449). CONCLUSIONS: QoL is significantly impaired in patients with AP who develop OFI. Nutritional management of acute pancreatitis needs to be optimized to prevent the occurrence of OFI.

Frequency of progression from acute to chronic pancreatitis and risk factors: a meta-analysis.

BACKGROUND & AIM: Acute pancreatitis (AP) and chronic pancreatitis (CP) traditionally have been thought to be distinct diseases, but there is evidence that AP can progress to CP. Little is known about the mechanisms of pancreatitis progression. We performed a meta-analysis to quantify the frequency of transition of AP to CP and identify risk factors for progression. METHODS: We searched PubMed, Scopus, and Embase for studies of patients with AP who developed CP, published from 1966 through November 2014. Pooled prevalence and 95% confidence intervals (CIs) were calculated for these outcomes, and sensitivity, subgroup, and meta-regression analyses were conducted. RESULTS: We analyzed 14 studies, which included a total of 8492 patients. The pooled prevalence of recurrent AP was 22% (95% CI, 18%-26%), and the pooled prevalence of CP was 10% (95% CI, 6%-15%). Sensitivity analyses yielded a pooled prevalence of CP of 10% (95% CI, 4%-19%) and 36% (95% CI, 20%-53%) in patients after the first occurrence and recurrent AP, respectively. Subgroup analyses found alcohol use and smoking to be the largest risk factors for the development of CP, with pooled prevalence values of 65% (95% CI, 48%-56%) and 61% (95% CI, 47%-73%), respectively. Meta-regression analysis found that men were more likely than women to transition from AP to CP. CONCLUSIONS: Ten percent of patients with a first episode of AP and 36% of patients with recurrent AP develop CP; the risk is higher among smokers, alcoholics, and men. Prospective clinical studies are needed to study pancreatitis progression.

Combining sensory information: mandatory fusion within, but not between, senses.

Humans use multiple sources of sensory information to estimate environmental properties. For example, the eyes and hands both provide relevant information about an object's shape. The eyes estimate shape using binocular disparity, perspective projection, etc. The hands supply haptic shape information by means of tactile and proprioceptive cues. Combining information across cues can improve estimation of object properties but may come at a cost: loss of single-cue information. We report that single-cue information is indeed lost when cues from within the same sensory modality (disparity and texture gradients in vision) are combined, but not when different modalities (vision and haptics) are combined.

How vertical disparities assist judgements of distance.

The ratio of the vertical sizes of corresponding features in the two eyes' retinal images depends both on the associated object's distance and on its horizontal direction relative to the head (eccentricity). It is known that manipulations of vertical size ratio can affect perceived distance, size, depth and shape. We examined how observers use the vertical size ratio to determine the viewing distance. Do they use the horizontal gradient of vertical size ratio, or do they combine the vertical size ratio itself with the eccentricity at which it is found? Distance scaling (as measured by having subjects set an ellipsoid's size and shape to match a tennis ball) was no better when the judged object was 30 degrees to the right of the head (where vertical size ratios vary considerably with distance) than when it was located straight ahead. Distance scaling improved when vertical disparities were presented within larger visual fields, irrespective of where this was relative to the head. Our results support the proposal that subjects use the horizontal gradient of vertical size ratio to estimate the distance of an object that they are looking at.

Ideal cue combination for localizing texture-defined edges.

Many visual tasks can be carried out by using several sources of information. The most accurate estimates of scene properties require the observer to utilize all available information and to combine the information sources in an optimal manner. Two experiments are described that required the observers to judge the relative locations of two texture-defined edges (a vernier task). The edges were signaled by a change across the edge of two texture properties [either frequency and orientation (Experiment 1) or contrast and orientation (Experiment 2)]. The reliability of each cue was controlled by varying the distance over which the change (in frequency, orientation, or contrast) occurred-a kind of "texture blur." In some conditions, the position of the edge signaled by one cue was shifted relative to the other ("perturbation analysis"). An ideal-observer model, previously used in studies of depth perception and color constancy, was fitted to the data. Although the fit can be rejected relative to some more elaborate models, especially given the large quantity of data, this model does account for most trends in the data. A second, suboptimal model that switches between the available cues from trial to trial does a poor job of accounting for the data.

Interaction of visual prior constraints.

The visual system relies on two types of information to interpret a visual scene: the cues that can be extracted from the retinal images and prior constraints that are used to disambiguate the scene. Many studies have looked at how multiple visual cues are combined. We examined the interaction of multiple prior constraints. The particular constraints studied here are assumptions the observer makes concerning the location of the light source (for the shading cue to depth) and the orientation of a surface (for depth based on image contours). The reliability of each of the two cues was manipulated by changing the contrast of different parts of the stimuli. We developed a model based on elements of Bayesian decision theory that permitted us to track the weights applied to each of the prior constraints as a function of the cue reliabilities. The results provided evidence that prior constraints behave just like visual cues to depth: cues with more reliable information have higher weight attributed to their corresponding prior constraint.

Long range interactions between oriented texture elements.

Long range interactions between texture elements (short, oriented line segments) were examined. Specifically, we studied the influence of a background array of texture elements on the detectability of a target element (separated from the background by an intermediate textured region) using textures like those of Caputo (Vis. Res. 1996, 36, 2815-2826). We found that, in general, when the background elements were oriented orthogonally to the target element, detection of the target element was better than when the background elements had the same orientation as the target element. We discuss these interactions in terms of inhibitory and excitatory connections between orientation and spatial frequency selective linear filters (e.g. filters which mimic V1 simple cells) which would respond to the individual texture elements.

Interaction between the perceived shape of two objects.

The difference between the way in which binocular disparity scales with viewing distance and the way in which motion parallax scales with viewing distance introduces a potential indirect cue for viewing distance: the viewing distance is the only distance at which disparity and motion specify the same depth. The present study examines whether this information is used. Two simulated ellipsoids were presented on a computer screen in complete darkness. The two ellipsoids were 6 degrees to the left and right of straight ahead. Subjects set the width and depth of each ellipsoid to match a tennis ball, and set the distance of the one on the right to half that of the one on the left. The distance of the left ellipsoid varied between trials. On half of the trials it was static. On the other half it was rotating up and down around its frontal horizontal axis. Rotating the left ellipsoid influenced its set depth: rotating ellipsoids were set to be much more spherical. There was no influence on the set depth of the other ellipsoid, or on the set width of either. The set distance of the right ellipsoid was also unaffected. We conclude that subjects do not combine binocular disparity and motion parallax to obtain more veridical information about viewing distance.

Observer biases in the 3D interpretation of line drawings.

Line drawings produced by contours traced on a surface can produce a vivid impression of the surface shape. The stability of this perception is notable considering that the information provided by the surface contours is quite ambiguous. We have studied the stability of line drawing perception from psychophysical and computational standpoints. For a given family of simple line drawings, human observers could perceive the drawings as depicting either an elliptic (egg-shaped) or hyperbolic (saddle-shaped) smooth surface patch. Rotation of the image along the line of sight and change in aspect ratio of the line drawing could bias the observer toward either interpretation. The results were modeled by a simple Bayesian observer that computes the probability to choose either interpretation given the information in the image and prior preferences. The model's decision rule is noncommitting: for a given input image its responses are still probabilistic, reflecting variability in the modeled observers' judgements. A good fit to the data was obtained when three observer assumptions were introduced: a preference for convex surfaces, a preference for surface contours aligned with the principal lines of curvature, and a preference for a surface orientation consistent with an object viewed from above. We discuss how these assumptions might reflect regularities of the visual world.

Examining edge- and region-based texture analysis mechanisms.

Instantaneous texture discrimination performance was examined for different texture stimuli to uncover the use of edge-based and region-based texture analysis mechanisms. Textures were composed of randomly placed, short, oriented line segments. Line segment orientation was chosen randomly using a Gaussian distribution (described by a mean and a standard deviation). One such distribution determined the orientations on the left side of the image, and a second distribution was used for the right side. The two textures either abutted to form an edge or were separated by a blank region. A texture difference in mean orientation led to superior discrimination performance when the textures abutted. On the other hand, when the textures differed in the standard deviation of the orientation distribution, performance was similar in the two conditions. These results suggest that edge-based texture analysis mechanisms were used (i.e. were the most sensitive) in the abutting difference-in-mean case, but region-based texture analysis mechanisms were used in the other three cases.

Suxamethonium and mivacurium sensitivity from pregnancy-induced plasma cholinesterase deficiency.

A fit 36-year-old parturient received a general anaesthetic for manual removal of a retained placenta. She underwent rapid sequence induction of anaesthesia with suxamethonium, shortly followed by 10 mg of mivacurium. One hour later she had failed to establish adequate ventilation despite administration of drugs to reverse neuromuscular blockade. A provisional diagnosis of suxamethonium-related apnoea was made and her lungs were ventilated overnight on the Intensive Care Unit. Plasma cholinesterase levels at the time were reduced to one-third of normal, with normal dibucaine and fluoride numbers. One month later her levels were back within the reference range.

Discrimination of orientation-defined texture edges.

Preattentive texture segregation was examined using textures composed of randomly placed, oriented line segments. A difference in texture element orientation produced an illusory, or orientation-defined, texture edge. Subjects discriminated between two textures, one with a straight texture edge and one with a "wavy" texture edge. Across conditions the orientation of the texture elements and the orientation of the texture edge varied. Although the orientation difference across the texture edge (the "texture gradient") is an important determinant of texture segregation performance, it is not the only one. Evidence from several experiments suggests that configural effects are also important. That is, orientation-defined texture edges are strongest when the texture elements (on one side of the edge) are parallel to the edge. This result is not consistent with a number of texture segregation models including feature- and filter-based models. One possible explanation is that the second-order channel used to detect a texture edge of a particular orientation gives greater weight to first-order input channels of that same orientation.