Depression Treatment Initiation Among Patients With Versus Without Chronic Pain.

OBJECTIVE: The purpose of this study was to examine the extent to which the presence of chronic noncancer pain (CNCP) impacts the likelihood that patients with diagnoses of depression will initiate depression treatment compared with those without CNCP. METHODS: We performed a retrospective cohort study of Kaiser Permanente of Georgia members older than 18 years who received a diagnosis of depression. Demographics and medical history were extracted from the electronic health record database. Members were further classified by the presence or absence of a CNCP diagnosis. Outcomes of interest were treated as time dependent and included ( 1 ) time to fulfillment of a new antidepressant medication and ( 2 ) time to a follow-up mental health encounter. Outcomes were compared between members with and without a CNCP diagnosis using Kaplan-Meier survival curves and Cox proportional hazard regression models. RESULTS: During the study period, 22,996 members met the inclusion criteria and 27.4% had a diagnosis of CNCP. In the matched sample, there was no difference in the time to a new antidepressant fill among members with and without CNCP (hazard ratio = 0.96; 95% confidence interval = 0.90-1.02; p = .18). In contrast, members with CNCP were significantly less likely to have a new mental health encounter after diagnosis (hazard ratio = 0.87; 95% confidence interval = 0.81-0.94; p < .001). CONCLUSIONS: Patients with CNCP were significantly less likely to have a new mental health encounter after a depression diagnosis compared with patients without CNCP. Additional outreach and consideration may be needed to improve initiation of depression treatment for newly diagnosed patients with comorbid depression and CNCP.

Factor Analysis in Distinguishing Coronavirus Disease 2019 From Other Influenza-like Illness Using a Validated Patient-Reported Outcome Instrument FLU-PRO Plus: A Prospective Real-world Cohort Study.

BACKGROUND/OBJECTIVE: InFLUenza Patient-reported Outcome (FLU-PRO Plus) is a 34-item patient-reported outcome instrument designed to capture the intensity and frequency of viral respiratory symptoms. This study evaluates whether FLU-PRO Plus responses could discriminate between symptoms of coronavirus disease 2019 (COVID-19) and influenza-like illness (ILI) with no COVID diagnosis, as well as forecast disease progression. METHODS: FLU-PRO Plus was administered daily for 14 days. Exploratory factor analysis was used to reduce the FLU-PRO Plus responses on the first day to 3 factors interpreted as "symptom clusters." The 3 clusters were used to predict COVID-19 versus ILI diagnosis in logistic regression. Correlation between the clusters and quality of life (QoL) measures was used to assess concurrent validity. The timing of self-reported return to usual health in the 14-day period was estimated as a function of the clusters within COVID-19 and ILI groups. RESULTS: Three hundred fourteen patients completed day 1 FLU-PRO Plus, of which 65% had a COVID-19 diagnosis. Exploratory factor analysis identified 3 symptom clusters: (1)general Body, (2) tracheal/bronchial, and (3) nasopharyngeal. Higher nasopharyngeal scores were associated with higher odds of COVID-19 compared with ILI diagnosis [adjusted odds ratio = 1.61 (1.21, 2.12)]. Higher tracheal/bronchial scores were associated with lower odds of COVID-19 [0.58 (0.44, 0.77)]. The 3 symptom clusters were correlated with multiple QoL measures ( r = 0.14-0.56). Higher scores on the general body and tracheal/bronchial symptom clusters were associated with prolonged time to return to usual health [adjusted hazard ratios: 0.76 (0.64, 0.91), 0.80 (0.67, 0.96)]. CONCLUSION: Three symptom clusters identified from FLU-PRO Plus responses successfully discriminated patients with COVID-19 from non-COVID ILI and were associated with QoL and predicted symptom duration.

Chronic pain diagnoses and opioid dispensings among insured individuals with serious mental illness.

BACKGROUND: Individuals with major depressive disorder (MDD) and bipolar disorder (BD) have particularly high rates of chronic non-cancer pain (CNCP) and are also more likely to receive prescription opioids for their pain. However, there have been no known studies published to date that have examined opioid treatment patterns among individuals with schizophrenia. METHODS: Using electronic medical record data across 13 Mental Health Research Network sites, individuals with diagnoses of MDD (N = 65,750), BD (N = 38,117) or schizophrenia or schizoaffective disorder (N = 12,916) were identified and matched on age, sex and Medicare status to controls with no documented mental illness. CNCP diagnoses and prescription opioid medication dispensings were extracted for the matched samples. Multivariate analyses were conducted to evaluate (1) the odds of receiving a pain-related diagnosis and (2) the odds of receiving opioids, by separate mental illness diagnosis category compared with matched controls, controlling for age, sex, Medicare status, race/ethnicity, income, medical comorbidities, healthcare utilization and chronic pain diagnoses. RESULTS: Multivariable models indicated that having a MDD (OR = 1.90; 95% CI = 1.85-1.95) or BD (OR = 1.71; 95% CI = 1.66-1.77) diagnosis was associated with increased odds of a CNCP diagnosis after controlling for age, sex, race, income, medical comorbidities and healthcare utilization. By contrast, having a schizophrenia diagnosis was associated with decreased odds of receiving a chronic pain diagnosis (OR = 0.86; 95% CI = 0.82-0.90). Having a MDD (OR = 2.59; 95% CI = 2.44-2.75) or BD (OR = 2.12; 95% CI = 1.97-2.28) diagnosis was associated with increased odds of receiving chronic opioid medications, even after controlling for age, sex, race, income, medical comorbidities, healthcare utilization and chronic pain diagnosis; having a schizophrenia diagnosis was not associated with receiving chronic opioid medications. CONCLUSIONS: Individuals with serious mental illness, who are most at risk for developing opioid-related problems, continue to be prescribed opioids more often than their peers without mental illness. Mental health clinicians may be particularly well-suited to lead pain assessment and management efforts for these patients. Future research is needed to evaluate the effectiveness of involving mental health clinicians in these efforts.

Assessing hand hygiene compliance among healthcare workers in six Intensive Care Units.

INTRODUCTION: Healthcare associated infections (HAIs) are a cause of high morbidity, disability and reduced quality of life, as well as mortality and rising costs for health systems. Preventing the HAI risk by planning and implementing effective preventive strategies is important to safeguard patient health. METHODS: The study aimed to evaluate the presence of procedures and protocols for infection control, to assess the adhesion to the different aspects of hand hygiene (HH) and hand washing technique by healthcare workers in six ICUs. A perspective observational study was conducted in six ICUs. In each ICU, the adherence by health care workers to both hand hygiene practices and standard precautions was assessed, as well as the presence of procedures and written protocols. RESULTS: The findings showed that in all the involved ICUs, 73 of 142 required protocols and procedures were available. Specifically, 59 of 79 were available for general measure of risk control, 12 of 15 for hand hygiene, and 24 of 48 for standard precautions and isolation measures. Also, the results showed highly variable levels of adherence to the best hygiene practices in all the ICUs involved in the study, with compliance rates ranging from 3% to 100%, and 73 of 142 required protocols were available at the study time. CONCLUSIONS: Overall, the involved ICUs showed low levels of adherence to best hygiene practices. This suggests the need to implement immediate strategies for infection control in the ICUs. A multidisciplinary intervention could be effective in preventing and control the HAI risk.score was reached only by the third year students with regard to the proper HH. The level of knowledge about HAI was inadequate.A periodically check of nursing students' knowledge would be advisable in order to fill any gaps, improve training, reduce HAI and increase prevention measures compliance.

Linezolid-induced thrombocytopenia in impaired renal function: is it time for a dose adjustment? A case report and review of literature.

PURPOSE: Thrombocytopenia is a common complication in the intensive care unit (ICU), but the incidence of drug-induced thrombocytopenia (DIT) is not well defined. We investigate linezolid-induced thrombocytopenia in patients with impaired renal function. Since recent studies suggest that linezolid clearance is reduced in these patients and there are no precise data confirming that dose-adjustment should be required, we performed a systematic analysis in order to establish whether it is necessary to consider a dose adjustment and promote studies to confirm this concept. METHODS: We report a case of thrombocytopenia (nadir 32 × 10(3)/µl) in a patient with acute kidney injury who was treated with linezolid for a MRSA pulmonary infection. We performed a systematic review of the literature through PubMed with the aim to include every case report, case series, prospective and retrospective clinical study reporting linezolid-induced thrombocytopenia with concomitant impaired renal function. RESULTS: An increasing number of clinical studies suggest a correlation between the onset of linezolid-induced thrombocytopenia and renal dysfunction. Close monitoring of platelet count and hemoglobin is recommended in patients treated with linezolid, especially in those with impaired renal function because the reduction of its clearance causes drug accumulation, as some studies have reported. CONCLUSIONS: Clinicians should consider the potential risk of this complication, especially in elderly patients with end-stage renal disease. Further studies should be encouraged to determine if the incidence of linezolid-related thrombocytopenia could be reduced by a dose adjustment according to renal function, for which currently there is still no specific recommendation.

Short report: Transition to International Classification of Diseases, 10th Revision and the prevalence of autism in a cohort of healthcare systems.

LAY ABSTRACT: Currently, the prevalence of autism spectrum disorder (henceforth "autism") is 1 in 36, an increasing trend from previous estimates. In 2015, the United States adopted a new version (International Classification of Diseases, 10th Revision) of the World Health Organization coding system, a standard for classifying medical conditions. Our goal was to examine how the transition to this new coding system impacted autism diagnoses in 10 healthcare systems. We obtained information from electronic medical records and insurance claims data from July 2014 through December 2016 for each healthcare system. We used member enrollment data for 30 consecutive months to observe changes 15 months before and after adoption of the new coding system. Overall, the rates of autism per 1000 enrolled members was increasing for 0- to 5-year-olds before transition to International Classification of Diseases, 10th Revision and did not substantively change after the new coding was in place. There was variation observed in autism diagnoses before and after transition to International Classification of Diseases, 10th Revision for other age groups. The change to the new coding system did not meaningfully affect autism rates at the participating healthcare systems. The increase observed among 0- to 5-year-olds is likely indicative of an ongoing trend related to increases in screening for autism rather than a shift associated with the new coding.

Acute nephrotoxicity of NSAID from the foetus to the adult.

NSAIDs are generally considered to be safe and well tolerated, but, even with the advent of selective COX-2 inhibitors, nephrotoxicity remains a concern. An impaired renal perfusion caused by the inhibition of prostaglandin synthesis is claimed like the more frequent cause of an acute renal failure due to NSAIDs, while a chronic interstitial nephritis or an analgesic nephropathy are believed the causes of a chronic renal failure. The real incidence of renal side effects of NSAIDs is still unclear and it differs between the age of the patients and the reports present in the literature. The occurrence of renal side effects following prenatal exposure to NSAIDs seems to be rare considering the large number of pregnant woman treated with indomethacin or other prostaglandin inhibitors. NSAID-related nephrotoxicity remains an important clinical problem in the newborns, in whom the functionally immature kidney may exert a significant effect on the disposition of the drugs. Instead, nephrotoxicity is a rare event in children and the risk is lower than adults. In healthy adult patients the incidence of renal adverse effects is very low, less than 1%. The risk increased with age. The elderly are at higher risk, and it is correlated at the presence of pretreatment renal disease, hypovolemia due to use of diuretics, diabetes, congestive heart failure or alteration of NSAID pharmacokinetics.

Factors Influencing Participation in Biospecimen Research among Parents of Youth with Mental Health Conditions.

INTRODUCTION: Biospecimens are tools that have the potential to improve early identification and treatment for autism spectrum disorders (ASD) and bipolar disorders (BPD). Unfortunately, most biobanks lack racial/ethnic diversity. One challenge to including a diverse sample of youth is recruiting and engaging families. OBJECTIVE: We sought to better understand facilitators and barriers to participation in biospecimen research among a diverse group of parents of youth with ASD and BPD. METHODS: The current study involved 3 Mental Health Research Network sites. At each site, parents participated in an interview that explored attitudes and beliefs about genetic research. Interviews were audio-recorded, and audio files were transcribed and coded using content analysis. RESULTS: A total of 58 interviews were conducted. Four challenges emerged: (1) contacting and engaging potential research participants, (2) motivating potential participants to read recruitment and consent materials, (3) motivating participation in research, in general, and (4) motivating participation in research involving biospecimen donation, specifically. CONCLUSIONS: Participants were eager to participate as long as the research process involved trust, clarity, and flexibility. Future research involving youth with mental health conditions would benefit from implementing multimodal strategies for recruitment and data collection and sharing knowledge gained by the research with study participants.

Controlling catheter-related bloodstream infections through a multi-centre educational programme for intensive care units.

BACKGROUND: Bloodstream infections (BSIs) associated with insertion and maintenance of central venous catheters (CRBSIs) are the most frequent causes of healthcare-associated infections in intensive care units (ICUs). They are responsible for increased length of hospital stay and additional healthcare costs. AIM: To investigate whether an educational programme aimed at healthcare workers resulted in a significant change in the level and trend of infections. METHODS: The research was conducted in five Italian ICUs from July 2012 to August 2014. Surveillance and educational interventions to control infections were applied. Compliance with hand hygiene procedures was assessed via relative risk and 95% confidence interval. Interrupted time-series analysis was used to investigate the change in level and trend of infection during the intervention. FINDINGS: Compliance with hand hygiene procedures improved during the intervention for all staff groups, but physicians showed the lowest compliance rates (nurses from 52.4% to 92.1%; nurse aides from 71.0% to 92%; physicians from 71.0% to 92%; P < 0.001). Significant reductions of 21-55% in CRBSI were observed during the intervention. Small improvements in the monthly infection trend were also observed, but these were not statistically significant. CONCLUSION: An educational programme focusing on general good infection control practice, rather than CVC care bundles, led to a decreased CRBSI rate, even if the improvement was not sustained over time. Continuous performance feedback should be provided to promote long-term adherence to guidelines among all health workers.

Pituitary apoplexy after laparoscopic surgery: a case report.

The occurrence of unprobable adverse events during laparoscopic surgery has increased over the years. Among them, pituitary apoplexy has been reported only twice. The increase in the abdominal pressure might play a role in the pituitary apoplexy, as well as hemodynamic instability, anticoagulant drugs and air-embolism due to insufflation of CO2 during pneumoperitoneum. We report a case of pituitary apoplexy during laparoscopic resection of sigmoid colon.

Is target opioid therapy within sight?

Control of pain has a central role in patients treatment either in advanced cancer or other terminal illnesses and in acute postsurgical or chronic non-malignant diseases. Hospitals should promote programs of research on genetic mechanism, and also biochemical and physiological aspects of pain through highly specialized labs. Opioids are the first choice drugs for moderate to severe chronic pain, especially at the end of life, and among them oral morphine is worldwide recognized by the World Health Organization and by the European Association for Palliative Care as the conventional therapy. Although this general agreement, administration of this class of drugs may be a major medical challenge due to the high effects' variability related to pharmacokinetic and pharmacodynamic parameters, such as absorption, distribution and metabolism, as well as intrinsic efficacy at the receptors involved. For such a reason, optimization of the management regime is not always reached in all the patients. Up to now no one can easily predict which patient will experience side effects or an inadequate pain control. The growing body of evidence concerning a sound genetic background of this human intervariability has prompted research on the field of a personalized therapy, focusing on single nucleotide polymorphisms (SNPs), being the most common and diffuse form of genetic variation. This review has the main goal to report the most promising human genetic polymorphisms involved in opioid treatment, and address the relationship between these polymorphisms and the clinical outcome.

Mitochondrial genome involvement in ischemia/reperfusion-induced adaptive changes in human myocardial cells.

AIM: Following previous studies on the ischemia-induced adaptive changes in human cardiac mitochondria, we examined in the present paper the interaction between nitric oxide-induced (NO) partial inhibition of Cyt. c oxidase (Cyt.OX) and mitochondrial encoded subunit 2 expression. Aim of the study was to investigate specific stages of the biochemical and molecular cascade which takes place in cytoprotective mechanisms of ischemic and reperfused cardiac cell. METHODS: We examined human left ventricle samples obtained from 20 patients undergoing elective valve surgery before aortic cross-clamping, 20+/-2 min (prolonged ischemia), 58+/-5 min after cross-clamping (intermittent ischemia) and 21+/-4 min after reconstitution of coronary blood flow (reperfusion). Cyt.OX activity was determined by spectrophotometric method and adenosine triphosphate (ATP) content using bioluminescent assay. Malondialdehyde (MDA) assumed as reactive oxygen species (ROS) generation marker was determined by high-performance liquid chromatography method. On the same cardiac samples mitochondrial encoded Cyt.OX subunit 2 expression was examined by immunoblot analysis and blu native gel electrophoresis method. Statistical study of obtained data was performed using repeated measures analysis of variance (ANOVA). RESULTS: Prolonged as well intermittent ischemia caused reduction of Cyt.OX activity and ATP, a moderate accumulation of ROS and down-regulation of Cyt.OX subunit 2. When reperfused the cardiomyocytes showed a progressive increase of Cyt.OX activity, ATP pools and Cyt.OX subunit 2 expression. ROS generation was significantly increased by the rapid oxygen re-immission in the cardiac cell. CONCLUSIONS: These data confirm the suggestion that prolonged as well as intermittent ischemia induces activation of cytoprotective mechanisms crucial for cardiac cell survival. Indeed, co-ordinated down-regulation of Cyt.OX activities, ATP pools and mitochondrial encoded Cyt.OX subunit 2 are in favour of an ischemia-activated adaptive mechanism leading to transient and reversible oxidative injury. This observation is confirmed by reduction of apoptosis molecular markers and by complete recovery of mitochondrial oxidative activities in reperfused cardiac tissue.

[Sudden infant death syndrome (SIDS): risk conditions and intervention strategies]. / Sudden infant death syndrome (SIDS): condizioni di rischio e strategie di intervento.

The term SIDS describes the unexpected and unexplained death of an apparently well infant. After congenital anomalies, SIDS is the most common cause of infant death in the industrial countries and it is the leading cause of death among infants older than 1 month. Descriptive epidemiological studies have shown a winter excess of cases and a peak of age distribution at about 3 months of age. Although many theories have been proposed to explain the etiology (i.e. fatal toxaemia, autonomic dysfunction, abnormalities of respiratory or cardiovascular control), an underlying cause for SIDS has not been identified. There are, however, a number of factors consistently associated with an elevated risk, the strongest of which are maternal smoking or exposure to substances of abuse during pregnancy, overheating and overinsulation, artificial feeding and prone sleeping position. A fall in the rate of the SIDS can be reasonably expected from changes in these risk factors, from home monitoring of infants suffering a near-SIDS episode and of siblings of SIDS victims, and from parental education programmes.

Immune reaction against the cytoskeleton in coeliac disease.

BACKGROUND: The cytoskeleton actin network of intestinal microvilli has been found to be rapidly impaired after gluten challenge in coeliac disease (CD). The aim of this study was to investigate the presence of an immune reaction towards cytoskeleton structures such as actin filaments in CD. METHODS: Eighty three antiendomysial antibody positive CD patients (52 children and 31 adults) were studied at our outpatient clinics from 1996 to 1998 using indirect immunofluorescence, ELISA, and western blotting for antiactin (AAA) and antitissue transglutaminase (TGA) antibodies before and after a gluten free diet (GFD). Sixteen patients with smooth muscle antibody positive autoimmune hepatitis, 21 with inflammatory bowel diseases, seven with small bowel bacterial overgrowth, and 60 healthy subjects were studied as controls. RESULTS: Fifty nine of 83 CD patients (28/31 adults (90.3%); 31/52 children (59.6%)) were positive for IgA and/or IgG AAA. Seventy seven (92.7%) were positive for IgA TGA. IgA AAA were strongly correlated with more severe degrees of intestinal villous atrophy (p<0.0001; relative risk 86.17). After a GFD, AAA became undetectable within five months. CONCLUSIONS: Apart from the immune reaction against the extracellular matrix, we have described an immune reaction against the cytoskeleton in both children and adults with CD. As AAA are strongly associated with more severe degrees of villous atrophy, they may represent a useful serological marker of severe intestinal atrophy in CD.

Early effects of gliadin on enterocyte intracellular signalling involved in intestinal barrier function.

BACKGROUND AND AIMS: Despite the progress made in understanding the immunological aspects of the pathogenesis of coeliac disease (CD), the early steps that allow gliadin to cross the intestinal barrier are still largely unknown. The aim of this study was to establish whether gliadin activates a zonulin dependent enterocyte intracellular signalling pathway(s) leading to increased intestinal permeability. METHODS: The effect of gliadin on the enterocyte actin cytoskeleton was studied on rat intestinal epithelial (IEC-6) cell cultures by fluorescence microscopy and spectrofluorimetry. Zonulin concentration was measured on cell culture supernatants by enzyme linked immunosorbent assay. Transepithelial intestinal resistance (Rt) was measured on ex vivo intestinal tissues mounted in Ussing chambers. RESULTS: Incubation of cells with gliadin led to a reversible protein kinase C (PKC) mediated actin polymerisation temporarily coincident with zonulin release. A significant reduction in Rt was observed after gliadin addition on rabbit intestinal mucosa mounted in Ussing chambers. Pretreatment with the zonulin inhibitor FZI/0 abolished the gliadin induced actin polymerisation and Rt reduction but not zonulin release. CONCLUSIONS: Gliadin induces zonulin release in intestinal epithelial cells in vitro. Activation of the zonulin pathway by PKC mediated cytoskeleton reorganisation and tight junction opening leads to a rapid increase in intestinal permeability.

Enterocyte actin autoantibody detection: a new diagnostic tool in celiac disease diagnosis: results of a multicenter study.

OBJECTIVES: This study describes a new method to detect autoantibodies against actin filaments (AAA) as a serological marker of intestinal villous atrophy (IVA) in celiac disease (CD), and reports the results of an Italian double-blind multicenter study. METHODS: IgA-AAA were analyzed by immunofluorescence using a newly developed method based on intestinal epithelial cells cultured in presence of colchicine. IgA-AAA were blindly evaluated prospectively in 223 antiendomysial antibody (AEA) and/or antitransglutaminase antibody (TGA) positive subjects and in 78 AEA and TGA negative subjects. IgA-AAA positive patients underwent an intestinal biopsy to confirm the diagnosis. Moreover, IgA-AAA were retrospectively investigated in 84 biopsy-proven CD patients and in 2,000 new consecutively collected serum samples from AEA and TGA negative nonbiopsied subjects. RESULTS: IgA-AAA were positive in 98.2% of the CD patients with flat mucosa, in 89% with subtotal villous atrophy, and in 30% with partial villous atrophy. IgA-AAA were present in none of the AEA and TGA negative nonbiopsied controls. In AEA and/or TGA positive CD patients IgA-AAA positivity significantly correlated with IVA (p < 0.000 in the prospective study, p = 0.005 in the retrospective study). In the prospective study, the values of sensitivity, specificity, the positive predictive value, the negative predictive value, and the efficiency of the IgA-AAA test to identify patients with IVA were, respectively, 83.9%, 95.1%, 97.8%, 69.2%, and 87.0%. Furthermore, a significant correlation (p < 0.0001) was found between the IgA-AAA serum titre and the degree of IVA (rs 0.56). CONCLUSIONS: The results of this multicenter study show that the new method for IgA-AAA detection could represent a practical diagnostic tool in AEA and/or TGA positive subjects, which would be especially useful when IVA shows a patchy distribution, when the histological picture is difficult to interpret, or when a biopsy could represent a life-threatening risk.