Computerized clinical decision support systems for acute care management: A decision-maker-researcher partnership systematic review of effects on process of care and patient outcomes

<p>Abstract</p> <p>Background</p> <p>Acute medical care often demands timely, accurate decisions in complex situations. Computerized clinical decision support systems (CCDSSs) have many features that could help. However, as for any medical intervention, claims that CCDSSs improve care processes and patient outcomes need to be rigorously assessed. The objective of this review was to systematically review the effects of CCDSSs on process of care and patient outcomes for acute medical care.</p> <p>Methods</p> <p>We conducted a decision-maker-researcher partnership systematic review. MEDLINE, EMBASE, Evidence-Based Medicine Reviews databases (Cochrane Database of Systematic Reviews, DARE, ACP Journal Club, and others), and the Inspec bibliographic database were searched to January 2010, in all languages, for randomized controlled trials (RCTs) of CCDSSs in all clinical areas. We included RCTs that evaluated the effect on process of care or patient outcomes of a CCDSS used for acute medical care compared with care provided without a CCDSS. A study was considered to have a positive effect (<it>i.e.</it>, CCDSS showed improvement) if at least 50% of the relevant study outcomes were statistically significantly positive.</p> <p>Results</p> <p>Thirty-six studies met our inclusion criteria for acute medical care. The CCDSS improved process of care in 63% (22/35) of studies, including 64% (9/14) of medication dosing assistants, 82% (9/11) of management assistants using alerts/reminders, 38% (3/8) of management assistants using guidelines/algorithms, and 67% (2/3) of diagnostic assistants. Twenty studies evaluated patient outcomes, of which three (15%) reported improvements, all of which were medication dosing assistants.</p> <p>Conclusion</p> <p>The majority of CCDSSs demonstrated improvements in process of care, but patient outcomes were less likely to be evaluated and far less likely to show positive results.</p

Cell Cycle Studies on the Human Nek3, Nek5 and Nek11 Protein Kinases

The NIMA-related kinases represent a family of serine/threonine protein kinases implicated in cell cycle control and ciliogenesis. The founding member of this family, the NIMA kinase of Aspergillus nidulans, contributes to multiple aspects of mitotic progression including the timing of mitotic entry, chromatin condensation, spindle organisation and mitotic exit. Mammals contain a family of eleven NIMA related kinases, named Nek1 to Nek11. Of these, to date there is substantial evidence that Nek2, Nek6, Nek7 and Nek9 regulate mitotic spindle formation, while Nek1 and Nek8 are implicated in microtubule organisation in non-dividing cells during ciliogenesis. The common underlying theme between spindle formation and ciliogenesis is the role of microtubules and microtubule organising centres. Hence, the emerging hypothesis is that all Neks may play a role in the organisation of microtubules. However, for several Neks, little if any information is available. In this thesis, I therefore began to examine the properties of three less well researched human Neks, Nek3, Nek5 and Nek11. First of all, antibodies against each of these kinases were generated or characterised. This allowed a broad study of the localisation, expression and activity of these kinases. Intriguingly, Nek3, Nek5 and Nek11 were all localised to centrosomes. Based on these results a more detailed study was performed with human Nek5 for which there is currently no published data. Human Nek5 is a nuclear protein that localises to the centrosomes during interphase, spindle poles during early mitosis, and to basal bodies in mono- ciliated cells. Specifically, Nek5 localised at the proximal ends of centrioles peaking in intensity in early mitosis. Importantly, siRNA-mediated depletion of Nek5 results in premature centrosome splitting and loss of centrosomal γ-tubulin. Hence, Nek5 is uncovered as a potential player in the negative regulation of centrosome separation

Cell cycle studies on the human Nek3, Nek5 and Nek11 protein kinases

The NIMA-related kinases represent a family of serine/threonine protein kinases implicated in cell cycle control and ciliogenesis. The founding member of this family, the NIMA kinase of Aspergillus nidulans, contributes to multiple aspects of mitotic progression including the timing of mitotic entry, chromatin condensation, spindle organisation and mitotic exit. Mammals contain a family of eleven NIMA related kinases, named Nek1 to Nek11. Of these, to date there is substantial evidence that Nek2, Nek6, Nek7 and Nek9 regulate mitotic spindle formation, while Nek1 and Nek8 are implicated in microtubule organisation in non-dividing cells during ciliogenesis. The common underlying theme between spindle formation and ciliogenesis is the role of microtubules and microtubule organising centres. Hence, the emerging hypothesis is that all Neks may play a role in the organisation of microtubules. However, for several Neks, little if any information is available. In this thesis, I therefore began to examine the properties of three less well researched human Neks, Nek3, Nek5 and Nek11. First of all, antibodies against each of these kinases were generated or characterised. This allowed a broad study of the localisation, expression and activity of these kinases. Intriguingly, Nek3, Nek5 and Nek11 were all localised to centrosomes. Based on these results a more detailed study was performed with human Nek5 for which there is currently no published data. Human Nek5 is a nuclear protein that localises to the centrosomes during interphase, spindle poles during early mitosis, and to basal bodies in mono- ciliated cells. Specifically, Nek5 localised at the proximal ends of centrioles peaking in intensity in early mitosis. Importantly, siRNA-mediated depletion of Nek5 results in premature centrosome splitting and loss of centrosomal γ-tubulin. Hence, Nek5 is uncovered as a potential player in the negative regulation of centrosome separation.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

“Because it is a rare disease…it needs to be brought to attention that there are things out of the norm”: a qualitative study of patient and physician experiences of Wilson disease diagnosis and management in the US

Abstract Background Wilson disease (WD) is a genetic disorder of copper metabolism that leads to copper accumulation in various organs, primarily the liver and brain, resulting in heterogenous hepatic, neurologic, and psychiatric symptoms. Diagnosis can occur at any age, requiring lifelong treatment, which can involve liver transplantation. This qualitative study aims to understand the wider patient and physician experience of the diagnosis and management of WD in the US. Methods Primary data were collected from 1:1 semi structured interviews with US-based patients and physicians and thematically analyzed with NVivo. Results Twelve WD patients and 7 specialist WD physicians (hepatologists and neurologists) were interviewed. Analysis of the interviews revealed 18 themes, which were organized into 5 overarching categories: (1) Diagnosis journey, (2) Multidisciplinary approach, (3) Medication, (4) The role of insurance, and (5) Education, awareness, and support. Patients who presented with psychiatric or neurological symptoms reported longer diagnostic journeys (range 1 to 16 years) than those presenting with hepatic symptoms or through genetic screening (range 2 weeks to 3 years). All were also affected by geographical proximity to WD specialists and access to comprehensive insurance. Exploratory testing was often burdensome for patients, but receipt of a definitive diagnosis led to relief for some. Physicians emphasized the importance of multidisciplinary teams beyond hepatology, neurology, and psychiatry and recommended a combination of chelation, zinc, and a low-copper diet; however, only half the patients in this sample were on a chelator, and some struggled to access prescription zinc due to insurance issues. Caregivers often advocated for and supported adolescents with their medication and dietary regimen. Patients and physicians recommended more education and awareness for the healthcare community. Conclusions WD requires the coordination of care and medication among several specialists due to its complex nature, but many patients do not have access to multiple specialties due to geographical or insurance barriers. Because some patients cannot be treated in Centers of Excellence, easy access to reliable and up-to-date information is important to empower physicians, patients, and their caregivers in managing the condition, along with general community outreach programs

Nek5 promotes centrosome integrity in interphase and loss of centrosome cohesion in mitosis

Nek5 is a poorly characterized member of the NIMA-related kinase family, other members of which play roles in cell cycle progression and primary cilia function. Here, we show that Nek5, similar to Nek2, localizes to the proximal ends of centrioles. Depletion of Nek5 or overexpression of kinase-inactive Nek5 caused unscheduled separation of centrosomes in interphase, a phenotype also observed upon overexpression of active Nek2. However, separated centrosomes that resulted from Nek5 depletion remained relatively close together, exhibited excess recruitment of the centrosome linker protein rootletin, and had reduced levels of Nek2. In addition, Nek5 depletion led to loss of PCM components, including gamma-tubulin, pericentrin, and Cdk5Rap2, with centrosomes exhibiting reduced microtubule nucleation. Upon mitotic entry, Nek5-depleted cells inappropriately retained centrosome linker components and exhibited delayed centrosome separation and defective chromosome segregation. Hence, Nek5 is required for the loss of centrosome linker proteins and enhanced microtubule nucleation that lead to timely centrosome separation and bipolar spindle formation in mitosis

Delphi panel to obtain clinical consensus about using long-acting injectable antipsychotics to treat first-episode and early-phase schizophrenia: treatment goals and approaches to functional recovery

Abstract Background Schizophrenia is mostly a chronic disorder whose symptoms include psychosis, negative symptoms and cognitive dysfunction. Poor adherence is common and related relapse can impair outcomes. Long-acting injectable antipsychotics (LAIs) may promote treatment adherence and decrease the likelihood of relapse and rehospitalization. Using LAIs in first-episode psychosis (FEP) and early-phase (EP) schizophrenia patients could benefit them, yet LAIs have traditionally been reserved for chronic patients. Methods A three-step modified Delphi panel process was used to obtain expert consensus on using LAIs with FEP and EP schizophrenia patients. A literature review and input from a steering committee of five experts in psychiatry were used to develop statements about patient population, adverse event management, and functional recovery. Recruited Delphi process psychiatrists rated the extent of their agreement with the statements over three rounds (Round 1: paper survey, 1:1 interview; Rounds 2–3: email survey). Analysis rules determined whether a statement progressed to the next round and the level of agreement deemed consensus. Measures of central tendency (mode, mean) and variability (interquartile range) were reported back to help panelists assess their previous responses in the context of those of the overall group. Results The Delphi panelists were 17 psychiatrists experienced in treating schizophrenia with LAIs, practicing in seven countries (France, Italy, US, Germany, Spain, Denmark, UK). Panelists were presented with 73 statements spanning three categories: patient population; medication dosage, management, and adverse events; and functional recovery domains and assessment. Fifty-five statements achieved ≥ 80% agreement (considered consensus). Statements with low agreement (40-79%) or very low agreement (< 39%) concerned initiating dosage in FEP and EP patients, and managing loss of efficacy and breakthrough episodes, reflecting current evidence gaps. The panel emphasized benefits of LAIs in FEP and EP patients, with consensus that LAIs can decrease the risk of relapse, rehospitalization, and functional dysfunction. The panel supported links between these benefits and multidimensional longer-term functional recovery beyond symptomatic remission. Conclusions Findings from this Delphi panel support the use of LAIs in FEP and EP schizophrenia patients regardless of disease severity, number of relapses, or social support status. Gaps in clinician knowledge make generating evidence on using LAIs in FEP and EP patients critical

Cephalic vein patency after deltopectoral approach to the shoulder and the effect on upper extremity edema

© 2020 American Shoulder and Elbow Surgeons Background: The effect of the direction of cephalic vein mobilization in a deltopectoral approach to the shoulder on limb edema is unknown. The primary objective was to evaluate the effect of the direction of cephalic vein mobilization/ligation on limb edema after elective shoulder arthroplasty. The secondary objectives were to: evaluate the effect of the arthroplasty procedure performed on limb edema; correlate postoperative ultrasonographic patency with intraoperative assessment. Methods: A cohort of 62 patients undergoing primary shoulder arthroplasty using the deltopectoral approach were enrolled and prospectively followed. Exclusion criteria included: surgery for fracture and prior open anterior shoulder procedure. Surgeons documented the direction of vein mobilization and if it was ligated. Patency was assessed by doppler ultrasound and standardized limb circumference measurement preoperatively, at 2 weeks and 12 weeks postoperatively. Results: Arm circumference was significantly increased at 2 weeks in all cohorts (lateral, p\u3c0.001; medial, p = 0.007; ligated, p = 0.011) and at 12 weeks in the laterally-mobilized (p = 0.022) and ligated cohorts (p = 0.003) as compared to preoperatively. Reverse shoulder arthroplasty demonstrated significantly greater arm circumference at 12 weeks as compared to total shoulder arthroplasty (p = 0.014). Intraoperative determination of patency was moderately correlated with 2- and 12-week (r = 0.70, 0.59) ultrasound assessment. Conclusion: Medial cephalic vein mobilization in a deltopectoral approach resulted in significantly less arm edema at 3-months when compared to lateral mobilization/ligation. Reverse shoulder arthroplasty demonstrated greater arm edema at 3-months when compared to total shoulder arthroplasty. Intraoperative determination of cephalic vein patency was moderately correlated with postoperative vein patency as assessed by ultrasound. Level of Evidence: III

Nek11S is required for G2/M checkpoint arrest and cell survival.

<p><b>A-L.</b> Using the protocols described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0140975#pone.0140975.g001" target="_blank">Fig 1A</a> for irradiation and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0140975#pone.0140975.g003" target="_blank">Fig 3A</a> for irinotecan treatment, HCT116 WT (A-C, G-I) and HCT116 p53-null (D-F, J-L) cells were transfected with siRNA oligonucleotides to co-deplete Nek11L and Nek11D (L/D), or deplete Nek11S or luciferase (siGL2). Histograms show the percentage of cycling cells at G2/M (A-F) and of total cells with sub-2n DNA (G-L). <i>p</i> values are relative to siGL2 for each treatment.</p

Nek5 promotes centrosome integrity in interphase and loss of centrosome cohesion in mitosis

Nek5 is a poorly characterized member of the NIMA-related kinase family, other members of which play roles in cell cycle progression and primary cilia function. Here, we show that Nek5, similar to Nek2, localizes to the proximal ends of centrioles. Depletion of Nek5 or overexpression of kinase-inactive Nek5 caused unscheduled separation of centrosomes in interphase, a phenotype also observed upon overexpression of active Nek2. However, separated centrosomes that resulted from Nek5 depletion remained relatively close together, exhibited excess recruitment of the centrosome linker protein rootletin, and had reduced levels of Nek2. In addition, Nek5 depletion led to loss of PCM components, including γ-tubulin, pericentrin, and Cdk5Rap2, with centrosomes exhibiting reduced microtubule nucleation. Upon mitotic entry, Nek5-depleted cells inappropriately retained centrosome linker components and exhibited delayed centrosome separation and defective chromosome segregation. Hence, Nek5 is required for the loss of centrosome linker proteins and enhanced microtubule nucleation that lead to timely centrosome separation and bipolar spindle formation in mitosis