Access control management in electronic health records: a systematic literature review

Objective

This study presents the results of a systematic literature review of aspects related to access control in electronic health records systems, wireless security and privacy and security training for users.

Methods

Information sources consisted of original articles found in Medline, ACM Digital Library, Wiley InterScience, IEEE Digital Library, Science@Direct, MetaPress, ERIC, CINAHL and Trip Database, published between January 2006 and January 2011. A total of 1,208 articles were extracted using a predefined search string and were reviewed by the authors. The final selection consisted of 24 articles.

Results

Of the selected articles, 21 dealt with access policies in electronic health records systems. Eleven articles discussed whether access to electronic health records should be granted by patients or by health organizations. Wireless environments were only considered in three articles. Finally, only four articles explicitly mentioned that technical training of staff and/or patients is required.

Conclusion

Role-based access control is the preferred mechanism to deploy access policy by the designers of electronic health records. In most systems, access control is managed by users and health professionals, which promotes patients’ right to control personal information. Finally, the security of wireless environments is not usually considered. However, one line of research is eHealth in mobile environments, called mHealth.     

Repeatability and agreement of ARK-30 autorefraction after cataract surgery

Background: To evaluate the intra‐test variability of ARK‐30 handheld autorefractor and the agreement with subjective refraction and retinoscopy after uneventful cataract surgery. Design: Prospective and non‐randomized study that included 6 visits by patients undergoing uneventful cataract surgery at IOBA (Instituto de Oftalmobiología Aplicada) Eye Institute (University of Valladolid). Participants: The mean age of the 79 patients was 66.5 years (range 23–90 years). For the 124 eyes, the mean spherical equivalent of the sample at baseline visit was ?3.59 ± 6.28 D (range ?21.00 D to +4.44 D). Methods: Automated refraction was performed on follow‐up visits 1 day and weekly for 4 weeks. Retinoscopy and subjective refraction were conducted at the Week 4 follow up. Main Outcome Measures: Automated refraction. Results: Sphere, cylinder and mean spherical equivalent, J₀ and J₄₅ coefficient variabilities were low in all visits. Standard deviations and the limits of agreement were smallest for the last visit. Subjective refraction sphere and cylinder values were more positive than autorefraction by 0.12 ± 0.53 D (P = 0.031) and 0.23 ± 0.42 D (P < 0.001), respectively. Comparison between autorefraction and retinoscopy showed a similar trend with the sphere and cylinder differences, 0.32 ± 0.77 D and 0.38 ± 0.43 D (P < 0.05), respectively. Conclusions: The ARK‐30 is sufficiently accurate and repeatable for automated refraction after uneventful cataract surgery. This instrument may be useful for monitoring refractive outcome in these patients.     

The Use of Pulse Oximetry to Determine Hypoxemia in Acute Exacerbations of COPD

Background: There is little evidence that the guideline-recommended oxygen saturation of 92% is the best cut-off point for detecting hypoxemia in COPD exacerbations. Objective: To detect and validate pulse oximetry oxygen saturation cut-off values likely to detect hypoxemia in patients with aeCOPD, to explore the correlation between oxygen saturation measured by pulse oximetry and hypoxemia or hypercapnic respiratory failure. Methodology: Cross-sectional study nested in the IRYSS-COPD study with 2,181 episodes of aeCOPD recruited between 2008 and 2010 in 16 hospitals belonging to the Spanish Public Health System. Data collected include determination of oxygen saturation by pulse oximetry upon arrival in the emergency department (ED), first arterial blood gasometry values, sociodemographic information, background medical history and clinical variables upon ED arrival. Logistic regression models were performed using as the dependent variables hypoxemia (PaO2 < 60 mmHg) and hypercapnic respiratory failure (PaO2 < 60 mmHg and PaCO2 > 45). Optimal cut-off points were calculated. Results: The correlation coefficient between oxygen saturation and pO2 measured by arterial blood gasometry was 0.89. The area under the curve (AUC) for the hypoxemia model was 0.97 (0.96–0.98) and the optimal cut-off point for hypoxemia was an oxygen saturation of 90%. The AUC for hypercapnic respiratory failure was 0.90 (0.87–0.92) and the optimal cut-off point was an oxygen saturation of 88%. Conclusions: Our results support current recommendations for ordering blood gasometry based on pulse oximetry oxygen saturation cut-offs for hypoxemia. We also provide easy to use formulae to calculate pO2 from oxygen saturation measured by pulse oximetry.     

Cyclin-dependent kinase 5 activates guanine nucleotide exchange factor GIV/Girdin to orchestrate migration–proliferation dichotomy

Signals propagated by receptor tyrosine kinases (RTKs) can drive cell migration and proliferation, two cellular processes that do not occur simultaneously—a phenomenon called “migration–proliferation dichotomy.” We previously showed that epidermal growth factor (EGF) signaling is skewed to favor migration over proliferation via noncanonical transactivation of Gαi proteins by the guanine exchange factor (GEF) GIV. However, what turns on GIV-GEF downstream of growth factor RTKs remained unknown. Here we reveal the molecular mechanism by which phosphorylation of GIV by cyclin-dependent kinase 5 (CDK5) triggers GIV''s ability to bind and activate Gαi in response to growth factors and modulate downstream signals to establish a dichotomy between migration and proliferation. We show that CDK5 binds and phosphorylates GIV at Ser1674 near its GEF motif. When Ser1674 is phosphorylated, GIV activates Gαi and enhances promigratory Akt signals. Phosphorylated GIV also binds Gαs and enhances endosomal maturation, which shortens the transit time of EGFR through early endosomes, thereby limiting mitogenic MAPK signals. Consequently, this phosphoevent triggers cells to preferentially migrate during wound healing and transmigration of cancer cells. When Ser1674 cannot be phosphorylated, GIV cannot bind either Gαi or Gαs, Akt signaling is suppressed, mitogenic signals are enhanced due to delayed transit time of EGFR through early endosomes, and cells preferentially proliferate. These results illuminate how GIV-GEF is turned on upon receptor activation, adds GIV to the repertoire of CDK5 substrates, and defines a mechanism by which this unusual CDK orchestrates migration–proliferation dichotomy during cancer invasion, wound healing, and development.Upon growth factor stimulation, cells initiate signaling cascades favoring either migration or proliferation (migration–proliferation dichotomy) depending on the extracellular environmental cues and/or cellular needs. This dichotomy (also known as “go-or-grow mechanism”) plays a crucial role during a variety of normal and pathophysiologic processes, including development, wound healing, and cancer progression (1–5).Of the multiple molecular mechanisms implicated in the orchestration of migration–proliferation dichotomy, Gα-interacting vesicle associated protein (GIV) (also known as Girdin) is one such player that helps tilt the signaling network to favor migration over proliferation downstream of stimulated growth factor receptors as well as G protein-coupled receptors (GPCRs) (6–12). In the case of EGF stimulation, GIV is recruited to the plasma membrane (PM) where it directly binds ligand-activated EGFR via its SH2-like domain (13) and serves as a platform for the assembly of receptor tyrosine kinase (RTK)-GIV-Gαi complexes and transactivation of Gαi via its guanine exchange factor (GEF) motif (8, 14). Such transactivation of Gi in the vicinity of RTKs at the PM enhances RTK autophosphorylation, prolongs RTK signaling from the PM, enhances PI3K/Akt signals and actin reorganization, and triggers cell migration (7–9, 13). Besides its role in the assembly of RTK-GIV-Gαi complexes at the PM, GIV also assembles EGFR-GIV-Gαs complexes on early endosomes where it facilitates down-regulation of EGFR via endosomal maturation, ensures finiteness of mitogenic signaling from that compartment, and limits cell proliferation (15).Much of the experimental evidence supporting GIV’s ability to skew the phenotypic response toward migration has been generated using a GEF-deficient mutant (F1685A, FA) of GIV, which cannot bind either Gαi at the PM or Gαs on endosomes (8, 15). Without the formation of RTK-GIV-Gαi/s complexes, ligand-activated EGFR spends a shorter time at the cell surface, but takes longer to transit through endosomes due to delayed endosomal maturation. Consequently, cells expressing GIV-FA suppress promigratory PI3K-Akt signals at the PM and enhance mitogenic signals from endosomes to preferentially trigger proliferation (8, 15). Despite the insights gained, the GIV-FA mutant did not illuminate how GIV-GEF may be reversibly switched “on/off” in physiology until recently, when that question was partially answered by the discovery of a key phosphoevent triggered by PKCθ at S1689 on GIV, which turns GIV-GEF “off” (16). However, what turns it “on” upon receptor activation still remained unknown.Here, we identify a key phosphoevent triggered by cyclin-dependent kinase 5 (CDK5) which turns on GIV''s GEF activity by phosphorylating it at Ser1674 and thereby increases GIV''s ability to bind Gαi/s and enhances its ability to activate Gαi. We provide mechanistic insight into how GIV-GEF is activated and also define a previously unidentified substrate by which CDK5 triggers cell migration. Thus, this study illustrates a physiologic event to activate GIV’s GEF function via a promigratory kinase, CDK5, which in turn dictates the orchestration of migration–proliferation dichotomy.     

Ethnic variation in the clinical manifestations of rheumatoid arthritis: Role of HLA–DRB1 alleles

Objective

To assess the extent of ethnic variation in the clinical expression of rheumatoid arthritis (RA) and the role of HLA–DRB1 alleles in this variation.

Methods

We assessed consecutive RA patients for joint findings, subcutaneous nodules, laboratory and radiographic findings, and treatment. We typed HLA–DRB1 alleles to identify those that contain the shared epitope (SE). We adjusted ethnic comparisons for age and sex, and tested for ethnic heterogeneity in the effect of the SE.

Results

We studied 777 RA patients, 498 of whom were women (64%), 432 were Hispanic (56%), 272 were non‐Hispanic white (NHW; 35%), 53 were African American (AA; 7%), and 20 were Asian (3%). Compared with NHW, Hispanics had significantly more tender joints (17 versus 11), more swollen joints (8 versus 7), more frequent rheumatoid factor (RF) positivity (93% versus 84%), higher erythrocyte sedimentation rate (ESR; 45 versus 36 mm/hr), and a lower number of lifetime disease‐modifying antirheumatic drugs (1.9 versus 2.5). AA were older at onset (46 versus 44 years), had less frequent subcutaneous nodules (18% versus 28%), and higher ESR (42 versus 36 mm/hour) than did NHW. Hispanics and AA were more likely than NHW to be null for the SE (odds ratio [OR] = 4.59 for AA; and OR = 1.61 for Hispanics), and less likely to have 2 SE‐carrying alleles (OR = 0.59 for Hispanics and OR = 0.25 for AA). The number of SE copies was associated with subcutaneous nodules, ESR, RF, and radiographic changes. Ethnic heterogeneity in the effect of the SE was modest.

Conclusions

There is ethnic variation in the clinical expression of RA and in both the frequency and types of SE‐carrying HLA–DRB1 alleles. Some ethnic variation in clinical findings is associated with differences in SE frequency. However, we found that the effect of the SE on the clinical features of RA varies little between ethnic groups.

     

Deficient phospholipase C activity in blood polimorphonuclear neutrophils from patients with liver cirrhosis

BACKGROUND/AIMS: Circulating neutrophils from cirrhotic patients have a reduced capacity to generate superoxide anion (O(2)(-)), which might contribute to frequent bacterial infections in these patients. We studied the signal transduction pathways involved in the generation of O(2)(-) in neutrophils from 98 cirrhotic patients and 46 healthy controls. METHODS: We measured O(2)(-) production in neutrophils induced by fMLP, opsonized zymosan, TNF alpha, NaF, AlF(4)(-), A23187 and phorbol myristate acetate. Furthermore, we measured phospholipase C activity in neutrophils from healthy controls and end-stage cirrhotic patients. RESULTS: O(2)(-) production was decreased in neutrophils from patients in response to fMLP, opsonized zymosan and TNF alpha. Likewise, response of these cells to G-protein stimulation by fluorides was also decreased. These reduced responses correlated significantly with the degree of liver dysfunction. On the contrary, neutrophils from patients responded normally to A23187 and phorbol esters stimulation indicating that Ca(2+)- and PKC-dependent pathways are intact in these cells. Finally, phospholipase C activity was markedly reduced in neutrophils from end-stage liver cirrhosis. CONCLUSIONS: These data confirm that O(2)(-) generation by neutrophils is decreased in patients with cirrhosis, particularly in those with more severe liver dysfunction, and suggest that this defect involves phosphatidylinositol specific phospholipase C activity.