A Survey of the Literature on Unintended Consequences Associated with Health Information Technology: 2014-2015.

OBJECTIVE: To summarize recent research on unintended consequences associated with implementation and use of health information technology (health IT). Included in the review are original empirical investigations published in English between 2014 and 2015 that reported unintended effects introduced by adoption of digital interventions. Our analysis focuses on the trends of this steam of research, areas in which unintended consequences have continued to be reported, and common themes that emerge from the findings of these studies. METHOD: Most of the papers reviewed were retrieved by searching three literature databases: MEDLINE, Embase, and CINAHL. Two rounds of searches were performed: the first round used more restrictive search terms specific to unintended consequences; the second round lifted the restrictions to include more generic health IT evaluation studies. Each paper was independently screened by at least two authors; differences were resolved through consensus development. RESULTS: The literature search identified 1,538 papers that were potentially relevant; 34 were deemed meeting our inclusion criteria after screening. Studies described in these 34 papers took place in a wide variety of care areas from emergency departments to ophthalmology clinics. Some papers reflected several previously unreported unintended consequences, such as staff attrition and patients' withholding of information due to privacy and security concerns. A majority of these studies (71%) were quantitative investigations based on analysis of objectively recorded data. Several of them employed longitudinal or time series designs to distinguish between unintended consequences that had only transient impact, versus those that had persisting impact. Most of these unintended consequences resulted in adverse outcomes, even though instances of beneficial impact were also noted. While care areas covered were heterogeneous, over half of the studies were conducted at academic medical centers or teaching hospitals. CONCLUSION: Recent studies published in the past two years represent significant advancement of unintended consequences research by seeking to include more types of health IT applications and to quantify the impact using objectively recorded data and longitudinal or time series designs. However, more mixed-methods studies are needed to develop deeper insights into the observed unintended adverse outcomes, including their root causes and remedies. We also encourage future research to go beyond the paradigm of simply describing unintended consequences, and to develop and test solutions that can prevent or minimize their impact.

Bilateral nocardial endophthalmitis in a prothonotary warbler (Protonotaria citrea).

A 7-year-old captive female prothonotary warbler (Protonotaria citrea) died following chronic feather and weight loss. At necropsy, the right eye had a 2 x 2 x 1 mm corneal plaque of inspissated yellow-tan material and edema of the lower eyelid. Microscopically, both eyes exhibited diffuse, severe pyogranulomatous endophthalmitis with retinal necrosis and detachment. Numerous intralesional branching, gram-positive, beaded, filamentous bacteria formed a thick mat attached to the retinal pigmented epithelium and extending into the pecten. Bacteria were strongly acid-fast positive by Fite's stain but only occasionally acid-fast positive by Ziehl-Neelsen staining, a characteristic consistent with a Nocardia spp. Infected regions demonstrated positive in situ hybridization reactivity with a probe complementary to the 16S rRNA gene of Nocardia spp. There was no evidence of primary bacterial infection in the other organs examined.

Stabilisation of scoliosis in two koi (Cyprinus carpio).

Two koi (Cyprinus carpio) from the same pond developed similar lesions of scoliosis. Radiographic examinations showed that their spines had become malaligned as a result of vertebral compression fractures involving T14 to T16. The vertebrae in both fish were stabilised with screws, k-wire and polymethylmethacrylate. They both appeared to improve after surgery, but they began to decline and died within three months. A postmortem examination revealed multi-organ inflammation that was not associated with the surgical implants.

Radiodermatitis after transjugular intrahepatic portosystemic shunt.

Transjugular intrahepatic portosystemic shunt (TIPS) is a recently introduced angiographic technique for achieving portal decompression. New invasive radiographic procedures such as TIPS can result in radiation exposure equal to that received by patients during radiation therapy. With these high doses of radiation, patients are at increased risk for radiodermatitis and long-term sequelae, such as scarring and carcinoma. Ours is the first reported case of radiodermatitis after TIPS.

Effects of light on the accumulation of abscisic acid and expression of an early cysteine-labeled metallothionein gene in microspores ofTriticum aestivum during induced embryogenic development.

A cloned cDNA to the wheat (Triticum aestivum) early cysteine-labeled metallothionein has many characteristics of a molecular marker for pollen embryogenesis in this plant. This transcript was not detected in uninucleate microspores at the time of culture or in pollen at any stage during normal ontogeny; its mRNA did begin to increase in embryogenic microspores within 6 h of culture, peaked at around 24 h, declined, then leveled off through the 21-day-old embryoid stage. Additionally, the accumulation of the embryoid-abundant EcMt gene transcript showed a direct and positive correlation with an increase of ABA in embryogenic microspores and developing pollen embryoids. Irradiating cultures with high intensity white light or with far-red, or blue light, suppressed EcMt transcript accumulation and the ability of microspores to form embryoids; however, light did not affect ABA concentrations during the early stages of culture. These results suggest that although a promoter of pollen embryogenesis in bread wheat, ABA alone cannot maintain the sporophytic differentiation of microspores subjected to inhibitory regimes of light in vitro. Whether or not light acts directly or indirectly in suppressing EcMt gene expression and pollen embryogenesis remains unknown.

Changes in abundance of an abscisic acid-responsive, early cysteine-labeled metallothionein transcript during pollen embryogenesis in bread wheat (Triticum aestivum).

A clone for an embryoid-abundant, early cysteine-labeled metallothionein (EcMt) gene has been isolated from a wheat pollen embryoid cDNA library. The transcript of this gene was only expressed in embryogenic microspores, pollen embryoids, and developing zygotic embryos of wheat. Accumulation of the EcMt mRNA showed a direct and positive correlation with an increase of the plant hormone, abscisic acid (ABA) in developing pollen embryoids. Treating cultures with an inhibitor of ABA biosynthesis, fluridone, suppressed not only ABA accumulation but also the appearance of the EcMt gene transcript and the ability of microspores to form embryoids. These results suggest that the EcMt gene may act as a molecular marker for pollen embryogenesis because ABA biosynthesis is accompanied by the increased expression of the EcMt transcript that coincides with the differentiation of pollen embryoids in wheat anther cultures.

Poisonous snakebite in Utah.

A retrospective study was done of poisonous snakebite in Utah to determine the current epidemiology and scope of treatment, reviewing emergency department logs and other sources statewide for a 69-month period. Of 61 cases of poisonous snakebite identified, 13 occurred in snake hobbyists or venom laboratory personnel and were considered nonaccidental, and 48 were inflicted by native noncaptive snakes. These bites were considered accidental, and all were presumed to be from rattlesnakes. Nearly three fourths of the victims were male, ranging in age from 2 to 56 years (mean, 22 years). Most accidental bites occurred in areas of high human populations, during the summer months, in the afternoon or evening hours, and during recreational activities. Of the 48 bites, 11 (23%) were provoked. Two thirds of bites were on the upper extremities, and a third were on the lower extremities. More than half of the victims had no first-aid treatment recorded. Of those who did receive first aid, many were subjected to possibly harmful treatments, including tourniquets and ice application. The median time to a hospital was 68 minutes, with a range of 15 to 440 minutes. Swelling and discoloration were the most common signs and pain and paresthesia the most common symptoms. Half the bites resulted in minimal or no envenomation, 17 (35%) produced moderate envenomation, and 6 (12%) severe envenomation. Most patients with moderate or severe envenomation received antivenin, but the dosages given were usually less than recommended dosages. Five patients received surgical treatment based on clinical findings. One child died in a snake-handling incident. Long-term morbidity was unknown due to lack of follow-up. The Utah Poison Control Center was poorly utilized as a reporting and informational resource.

A small GTP-binding protein from Arabidopsis thaliana functionally complements the yeast YPT6 null mutant.

A clone designated A.t.RAB6 encoding a small GTP-binding protein was isolated from a cDNA library of Arabidopsis thaliana leaf tissue. The predicted amino acid sequence was highly homologous to the mammalian and yeast counterparts, H.Rab6 and Ryh1/Ypt6, respectively. Lesser homology was found between the predicted Arabidopsis protein sequence and two small GTP-binding proteins isolated from plant species (44% homology to Zea mays Ypt1 and 43% homology to Nicotiana tabacum Rab5). Conserved stretches in the deduced amino acid sequence of A.t.Rab6 include four regions involved in GTP-binding, an effector region, and C-terminal cysteine residues required for prenylation and subsequent membrane attachment. Northern blot analysis demonstrated that A.t.Rab6 mRNA was expressed in root, leaf, stem, and flower tissues from A. thaliana with the highest levels present in roots. Escherichia coli produced histidine-tagged A.t.Rab6 protein-bound GTP, whereas a mutation in one of the guanine nucleotide-binding sites (asparagine122 to isoleucine) rendered it incapable of binding GTP. Functionally, the A.t.RAB6 gene was able to complement the temperature-sensitive phenotype of the YPT6 null mutant in yeast. The isolation of this gene will aid in the dissection of the machinery involved in soluble protein sorting at the trans-Golgi network of plants.

Identification of Embryoid-Abundant Genes That Are Temporally Expressed during Pollen Embryogenesis in Wheat Anther Cultures.

Uninucleate microspores in anther cultures of bread wheat (Triticum aestivum cv Pavon) are capable of producing haploid pollen embryoids and plants. To gain an understanding of this alternate pathway of pollen development, we constructed a cDNA library to young pollen embryoids, isolated embryoid-specific genes, and analyzed their expression patterns during morphogenesis. Two embryoid-abundant clones, pEMB4 and 94, were expressed very early during culture, suggesting that these genes are associated with development and are not simply expressed as a consequence of differentiation. The accumulation patterns of five cloned mRNAs may indicate the activation of specific genes associated with the major morphological and physiological activities connected with the differentiation of embryoids in vitro. These results suggest that embryoid-abundant gene expression is causally related to this pathway because gene expression is spatially and temporally specific and is not observed when microspores are cultured under noninductive conditions.

Differences in HLA-B27 positive and negative patients with ankylosing spondylitis: study of clinical disease activity and concentrations of serum IgA, C reactive protein, and haptoglobin.

To find out whether disease activity and B27 status were associated with serum concentrations of IgA, C reactive protein (CRP), and haptoglobin in ankylosing spondylitis (AS) multivariate analysis of variance was used to study 101 patients with AS whose disease was clinically classified as active or inactive, and who were HLA-B27 typed. It was found that B27 and disease activity do interact significantly to affect the serum concentrations of IgA, CRP, and haptoglobin. When the 77 B27+ patients were examined, however, it was found that disease activity was significantly associated with serum concentrations IgA. In contrast, in the 24 B27- patients concentrations of serum IgA were significantly associated with disease activity, but not. These results emphasise the known difference between B27+ and B27- AS and suggest different pathogenic mechanisms in the two forms of AS.

Effect of preincubation temperature on in vitro light saturated photosystem I activity in thylakoids isolated from cold hardened and nonhardened rye.

Thylakoids isolated from winter rye (Secale cereale L. cv Muskateer) grown at 5 degrees C or 20 degrees C were compared with respect to their capacity to exhibit an increase in light saturated rates of photosystem I (PSI) electron transport (ascorbate/dichlorophenolindophenol --> methylviologen) after dark preincubation at temperatures between 0 and 60 degrees C. Thylakoids isolated in the presence or absence of Na(+)/Mg(2+) from 20 degrees C grown rye exhibited transient, 40 to 60% increases in light saturated rates of PSI activity at all preincubation temperatures between 5 and 60 degrees C. This increase in PSI activity appeared to occur independently of the electron donor employed. The capacity to exhibit this in vitro induced increase in PSI activity was examined during biogenesis of rye thylakoids under intermittent light conditions at 20 degrees C. Only after exposure to 48 cycles (1 cycle = 118 minutes dark + 2 min light) of intermittent light did rye thylakoids exhibit an increase in light saturated rates of PSI activity even though PSI activity could be detected after 24 cycles. In contrast to thylakoids from 20 degrees C grown rye, thylakoids isolated from 5 degrees C grown rye in the presence of Na(+)/Mg(2+) exhibited no increase in light saturated PSI activity after preincubation at any temperature between 0 and 60 degrees C. This was not due to damage to PSI electron transport in thylakoids isolated from 5 degrees C grown plants since light saturated PSI activity was 60% higher in 5 degrees C thylakoids than 20 degrees C thylakoids prior to in vitro dark preincubation. However, a two-fold increase in light saturated PSI activity of 5 degrees C thylakoids could be observed after dark preincubation only when 5 degrees C thylakoids were initially isolated in the absence of Na(+)/Mg(2+). We suggest that 5 degrees C rye thylakoids, isolated in the presence of these cations, exhibit light saturated PSI electron transport which may be closer to the maximum rate attainable in vitro than 20 degrees C thylakoids and hence cannot be increased further by dark preincubation.

Low growth temperature-induced increase in light saturated photosystem I electron transport is cation dependent.

Thylakoid membranes isolated from cold tolerant, herbaceous monocots and dicots grown at 5 degrees C exhibit a 1.5-fold to 2.7-fold increase in light saturated rates of photosystem I (PSI) electron transport compared to thylakoids isolated from the same plant species grown at 20 degrees C. This was observed only when either water or reduced dichlorophenolindophenol was used as an electron donor. The apparent quantum yield for PSI electron transport was not affected by growth temperature. The higher light saturated rates of PSI electron transport in 5 degrees C thylakoids had an absolute requirement for the presence of Na(+) and Mg(+2). The accessibility of reduced dichlorophenolindophenol to the donor site was not affected by growth temperature since 5 degrees C and 20 degrees C thylakoids exhibited no significant difference in the concentration of this electron donor required for half-maximal PSI activity. The cation dependent higher rates of light saturated PSI activity were also observed when rye thylakoids were developed under intermittent light conditions at 5 degrees C. Thus, this cation effect on PSI activity appeared to be independent of light harvesting complex I and II. The extent of the in vitro reversibility of this cation effect appeared to be limited by an inherent decay process for PSI electron transport. The rate of decay for PSI activity was greatest when thylakoids were isolated in the absence of NaCl and MgCl(2). We conclude that exposure of plants to low growth temperatures induces a reorganization of thylakoid membranes which increases the light saturated rates of PSI electron transport with no change in the apparent quantum efficiency for this reaction. Cations are required to stabilize this reorganization.

Familial occurrence of systemic sclerosis, rheumatoid arthritis and other immunological disorders: report of two kindreds with study of HLA antigens and review of the literature.

We report two Caucasian families with systemic sclerosis and other connective tissue and immunological disorders, including rheumatoid arthritis, discoid lupus erythematosus, psoriasis, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis, asthma, Sjögren's syndrome, Raynaud's phenomenon and thyroid disease. In one of these families, two sisters are affected with systemic sclerosis. Clinical, serological, and HLA haplotype results are reported, along with a review of the medical literature on familial occurrence of systemic sclerosis.

Serum IgA, acute phase proteins, and glycosylation of alpha 1-acid glycoprotein in ankylosing spondylitis.

Several investigators have suggested that gastrointestinal inflammation has a role in the pathogenesis of ankylosing spondylitis. To test this hypothesis markers of gastrointestinal immunostimulation, as manifested by serum IgA concentrations, were compared with serum markers of inflammation, as manifested by acute phase proteins. Serum samples from 45 unrelated Caucasian patients with ankylosing spondylitis (AS) were tested for correlation of serum IgA and six acute phase proteins: C reactive protein (CRP), alpha 1-antitrypsin, alpha 1-antichymotrypsin, caeruloplasmin, alpha 1-acid glycoprotein (AGP), and haptoglobin. Serum IgA was shown to be significantly positively correlated with four of these six acute phase proteins: CRP (r = 0.58, p less than 0.001), alpha 1-antitrypsin (r = 0.29, p less than 0.05), AGP (r = 0.61, p less than 0.01), and haptoglobin (r = 0.58, p less than 0.001), suggesting that gastrointestinal immunostimulation does have a role in the pathogenesis of inflammation in AS. In addition, the microheterogeneity of the pattern of glycosylation of AGP, expressed as reactivity coefficients, was examined. The AGP reactivity coefficient has been shown to increase in infection, remain the same in systemic lupus erythematosus, and decrease in rheumatoid arthritis. It was found that the AGP reactivity coefficient was significantly decreased in patients with AS as compared with healthy controls (p less than 0.006). As recent studies have indicated that patterns of glycosylation reflect intrahepatocellular biosynthetic processes induced by cytokines our data suggest that cytokine-hepatocellular mechanisms in AS may be similar to those occurring in rheumatoid arthritis, but different from those in systemic lupus erythematosus or infection.

Herpes encephalitis: MR monitoring of response to acyclovir therapy.

Viral encephalitis secondary to herpes simplex virus type I is thought to be the single most important cause of fatal, sporadic encephalitis in the United States. Magnetic resonance not only improves early diagnosis of herpes encephalitis but also is effective in documenting response to antiviral therapy.