Antibodies to calnexin and mutated calreticulin are common in human sera.

PURPOSE OF THE STUDY: Calreticulin is an endoplasmic reticulum chaperone protein, which is involved in protein folding and in peptide loading of major histocompatibility complex class I molecules together with its homolog calnexin. Mutated calreticulin is associated with a group of hemopoietic disorders, especially myeloproliferative neoplasms. Currently only the cellular immune response to mutated calreticulin has been described, although preliminary findings have indicated that antibodies to mutated calreticulin are not specific for myeloproliferative disorders. These findings have prompted us to characterize the humoral immune response to mutated calreticulin and its chaperone homologue calnexin. PATIENTS AND METHODS: We analyzed sera from myeloproliferative neoplasm patients, healthy donors and relapsing-remitting multiple sclerosis patients for the occurrence of autoantibodies to wild type and mutated calreticulin forms and to calnexin by enzyme-linked immunosorbent assay. RESULTS: Antibodies to mutated calreticulin and calnexin were present at similar levels in serum samples of myeloproliferative neoplasm and multiple sclerosis patients as well as healthy donors. Moreover, a high correlation between antibodies to mutated calreticulin and calnexin was seen for all patient and control groups. Epitope binding studies indicated that cross-reactive antibodies bound to a three-dimensional epitope encompassing a short linear sequence in the C-terminal of mutated calreticulin and calnexin. CONCLUSION: Collectively, these findings indicate that calreticulin mutations may be common and not necessarily lead to onset of myeloproliferative neoplasm, possibly due to elimination of cells with mutations. This, in turn, may suggest that additional molecular changes may be required for development of myeloproliferative neoplasm.

Suicide and death by other causes among patients with a severe mental illness: cohort study comparing risks among patients discharged from inpatient care v. those treated in the community.

AIMS: People diagnosed with a severe mental illness (SMI) are at elevated risk of dying prematurely compared to the general population. We aimed to understand the additional risk among people with SMI after discharge from inpatient psychiatric care, when many patients experience an acute phase of their illness. METHODS: In the Clinical Practice Research Datalink (CPRD) GOLD and Aurum datasets, adults aged 18 years and older who were discharged from psychiatric inpatient care in England between 2001 and 2018 with primary diagnoses of SMI (schizophrenia, bipolar disorder, other psychoses) were matched by age and gender with up to five individuals with SMI and without recent hospital stays. Using survival analysis approaches, cumulative incidence and adjusted hazard ratios were estimated for all-cause mortality, external and natural causes of death, and suicide. All analyses were stratified by younger, middle and older ages and also by gender. RESULTS: In the year after their discharge, the risk of dying by all causes examined was higher than among individuals with SMI who had not received inpatient psychiatric care recently. Suicide risk was 11.6 times (95% CI 6.4-20.9) higher in the first 3 months and remained greater at 2-5 years after discharge (HR 2.3, 1.7-3.2). This risk elevation remained after adjustment for self-harm in the 6 months prior to the discharge date. The relative risk of dying by natural causes was raised in the first 3 months (HR 1.6, 1.3-1.9), with no evidence of elevation during the second year following discharge. CONCLUSIONS: There is an additional risk of death by suicide and natural causes for people with SMI who have been recently discharged from inpatient care over and above the general risk among people with the same diagnosis who have not recently been treated as an inpatient. This mortality gap shows the importance of continued focus, following discharge, on individuals who require inpatient care.

Prosthodontic management of maxillofacial cases: a case series.

Maxillofacial prosthetics is an important and recognized sub-discipline of prosthodontics that forms a key component of postgraduate training programmes. General dentists have a role to play in the management of maxillofacial defect patients even though treatment usually requires a multidisciplinary approach in an institutional environment. Maxillofacial prosthetic cases frequently present with complex histories but simple patient goals. The conservatively managed implant-retained auricular prosthesis, speech aid prosthesis and orbital prosthesis cases described in this report were completed in a postgraduate clinical residency program and highlight the intrinsic complexities, challenges and ultimately satisfaction related to cases of this nature.

Comparing preferences for outcomes of psoriasis treatments among patients and dermatologists in the U.K.: results from a discrete-choice experiment.

BACKGROUND: Plaque psoriasis can have a significant negative effect on patients' quality of life, and treatments can result in serious toxicities. Although there have been several studies of patients' and physicians' relative preferences for the benefits and risks of psoriasis treatments, it is unclear how and whether patients' and physicians' preferences for the outcomes of psoriasis treatments differ. OBJECTIVES: To quantify patient and dermatologist preferences for improvements in psoriasis symptoms and for increases in the risk of treatment-related serious adverse events. METHODS: Members of the U.K. Psoriasis Association and U.K. dermatologists with experience prescribing biologics completed a web-enabled discrete-choice experiment survey in which they evaluated efficacy and safety features of biological treatments for psoriasis. Choices between hypothetical treatment options were used to estimate preference weights indicating respondents' relative trade-off preferences among treatment outcomes. These outcomes included improvements in the severity and coverage of psoriatic plaques and treatment-related risks of tuberculosis, serious infections and lymphoma. Preference estimates were used to derive the maximum level of side-effect risks that respondents would accept for improvements in psoriasis symptoms. RESULTS: Respondents' tolerance for side-effect risks varied with side-effect severity and location of plaques, and risk tolerance for serious side-effects was greater for patients than for dermatologists. CONCLUSIONS: Estimates of patients' risk tolerance for serious side-effects indicate that patients valued psoriasis symptom control highly and suggest that psoriasis symptoms have a significant effect on patients' quality of life. In light of research showing increased treatment satisfaction and improved treatment adherence among patients who receive therapies that are consistent with their preferences, our findings suggest that greater communication between dermatologists and patients about risk tolerance could help improve patient care.

To re-emphasize the need for fluoride in blood samples for glucose-level testing.

Blood samples were collected from 30 subjects. To a portion from each sample was added Fluoride/Ethylene Diamine Tetra Acetate (E.D.T.A) to inhibit glycolysis and clotting. The remaining portions were allowed to clot without any inhibitor. On subjecting to glucose concentration testing, the portions without the inhibitor showed a decline in the glucose level of 8 mg/dl (0.44 mmol/l) in the first hour and of 7 mg/dl (0.39 mmol/l) per hour in the next two hours. It is re-emphasised that a glycolysis inhibitor should always be added to blood samples drawn for glucose level testing. Otherwise, the reported results could be misleading.

A study of the accuracy of the Precision Q.I.D. glucometer.

The Precision Quantum-in-dium (Q.I.D.) Glucometer was used to determine the glucose concentrations of 38 human blood samples. The same samples were also run on the OPERA Chemistry Autoanalyzer 2010 system. More than 44% of the glucometer reports had a difference of greater than 15% from the respective autoanalyzer reports. The calibration of the glucometer could be the source of the error and an improvement is recommended.