Development of UHPLC-MS/MS methods to quantify 25 antihypertensive drugs in serum in a cohort of patients treated for hypertension

We developed three ultra-high pressure liquid chromatography coupled to mass spectrometry detection (UHPLC-MS/MS) methods to quantify 25 antihypertensive drugs in serum samples. Patient-reported drug lists were collected, and drug concentrations were analysed in samples from 547 patients, half with uncontrolled hypertension, and all treated with ≥ 2 antihypertensive drugs. For sample preparation, serum was mixed with deuterated internal standards and acetonitrile and precipitated. Aliquots of the supernatant were injected on UHPLC-MSMS with a C18 reversed phase column. The mobile phase was 0.1 % HCOOH (formic acid) in water and 0.1 % HCOOH in acetonitrile (except in methanol for spironolactone/canrenone) at a flow rate of 0.4 mL/min. The calibrators and internal controls were prepared in Autonorm™. The calibration ranges were wide, and the models were linear or quadratic with squared correlation coefficients ≥ 0.97. The limits of detection and quantification, specificity, carry-over, and matrix effects were acceptable. The accuracy of the internal controls was in the range 85–121 %, and the intermediate precision for all drugs was 4–28 %. The patient-reported antihypertensive drug use and the detected serum drug concentrations were in accordance with that most frequently prescribed nationally. The percent non-detectable level was 5–10 % for bendroflumethiazide, doxazosin, nifedipine, and ramipril. Often the drug dose chosen was lower than the recommended maximum daily dose. We report the maximum (Cmax) and minimum (Cmin) drug concentrations after drug intake. The inter-individual pharmacokinetic variability at Cmin was 18-fold for hydrochlorothiazide, 22-fold for losartan carboxyl acid, 26-fold for amlodipine, 44-fold for candesartan, and 50-fold for valsartan. Our methods are suitable for measuring antihypertensive drugs in patient serum for therapy control.publishedVersio

Scintigrafic evaluation of aortacoronary revascularization inhospital

Objective- The diagnosis of perioperative myocardial infarction (PMI) after coronary artery bypass graft surgery (CABG) is difficult because there is no consensus on the criteria, and silent ischemia may be difficult to detect. The purpose of the SCENARIO study was to evaluate the use of 99mTechnetium-tetrofosmin myocardial perfusion tomography (SPECT) at rest in the diagnosis of PMI and reversible ischemia after CABG. Design- We did a prospective trial of 102 patients undergoing elective CABG surgery. The patients were randomized into two groups. 48 patients underwent traditional management with serial ECG recordings and measurements of CK-MB, CK and Troponin T postoperatively. 54 patients were additionally examined with myocardial scintigraphy preoperatively, and 2-4 days and 6 weeks postoperatively. Results and discussion- Based on different ECG and biochemical marker criteria, we found an incidence of PMI between 2,9-6,9%. In addition, 5 other patients had scintigraphic findings of PMI, as measured by the hypoperfusion index (HPI).This may represent subendocardial infarctions, without significant changes in ECG. Overall the study group showed a highly significant improvement in myocardial perfusion after CABG. No significant change in HPI was observed from 2-4 days to 6 weeks postoperatively. 15 patients had a gradual reduction in HPI that may be due to stunning or hibernating myocardium. Conclusion- Our results show that SPECT can detect more cases of reversible and irreversible ischemia after CABG, than ECG and biochemical markers. However, further data processing is needed to draw final conclusions in the SCENARIO study

Digital affärsmodellsutveckling för fysiska butiker

På senare tid har fysiska butiker hamnat alltmer i skuggan av stora digitala handelsplattformar som CDON eller Amazon och tomma butikslokaler är en allt vanligare syn runtom i Sverige. Som en motreaktion på detta har näringslivsföreningen i Torsby kommun startat ett samarbete där fysiska butiker i kommunen erbjuds möjligheten att ansluta sig till en lokal digital handelsplattform. En av anledningarna till detta är att göra Torsbys butiker mera tillgängliga och på så vis fånga upp kunder som önskar handla lokalt på ett digitalt och bekvämt sätt.  Syftet med studien är att beskriva hur en fysisk butiks affärsmodell kan utvecklas för att möta kundernas alltmer digitala köpbeteende. Projektet som beskrivs ovan går under namnet handla.itorsby.se och är hela studiens nav. En relevant frågeställning är förstås om denna digitala handelsplattform kan hjälpa butikerna i Torsby från att tyna bort? Det finns naturligtvis otaliga sätt att angripa frågor som denna på men vi har valt att titta närmare på butikernas affärsmodeller. Att kontinuerligt arbeta med affärsmodellsutveckling är viktigt men åsidosätts ofta bland företag (Chesbrough, 2007). En av anledningarna kan vara att medveten affärsmodellsutveckling är ett relativt outforskat område (Fjeldstad & Snow, 2018) och tillvägagångsätten för denna process är abstrakta och svårförståeliga.  Studien finner att den digitala handelsplattformen har potentialen att utveckla och förändra de anslutna butikernas affärsmodeller och således motverka eroderingen av dessa. Vägen dit är dock i skrivande stund lång, detta på grund av två anledningar. Nummer ett: den digitaliseringsgrad som krävs för att butiken ska vara en fungerande del av handelsplattformen är, för de flesta, långt ifrån verklighet. Nummer två: det råder en viss tvetydighet om vad syftet med handelsplattformen verkligen är. Näringslivsföreningen menar att projektet går ut på att utbilda samt digitalisera butikerna i Torsby. Kunderna ser handelsplattformen som vilken digital handelsplats som helst och förväntar sig således att den ska fungera som en sådan. Butikerna pendlar mellan dessa två ytterligheter, vissa ser projektet som en chans att utbilda och digitalisera sin verksamhet andra ser det som ytterligare en säljkanal. Plattformen har, som tidigare nämnts, potentialen att utveckla och förändra butikernas affärsmodeller, men för att detta ska bli verklighet så måste syftet vara mer förankrat hos butikerna själva. Många är helt enkelt inte redo för en sådan förändring.  During recent times physical stores have found it hard to survive, which is made noticeable by all the empty shop premises around the country. The reasons are many, but the increasing competition from internet commerce is one of the more severe ones. Many of our respondents experience this competition when the pressure from digital platforms such as Amazon becomes more palpable.  Digital business model development regarding physical stores has been neglected in business model research. Therefore, the purpose of this study is to describe how a physical stores business model can develop to meet the customers' increasingly digital buying behavior. In this study, we have looked closer at the digital business platform: handla.itorsby.se trying to understand if this digital tool can help physical stores to regain some competitiveness. We look at this problem from a business model perspective. To work continuously with business model development is significant but often disregarded. It is crucial since business models lose their relevance as time goes by. The study concludes that the platform is not particularly helpful in developing and changing the physical stores’ business models. There are two main reasons for this. Number one: The degree to which the organizations are up to date digitally. Many of the companies are too far behind digitally to be an active part of the platform. The change needed in their business model is far too radical. These companies' business models have been static for a long time and focused on developing and changing the internal operational processes that are a part of the business. The dynamics of the business model have not changed or developed at all. Therefore, their business models are considered outdated.  The second reason is that there is an ambiguity regarding what role the business platform has. From the project management perspective, the goal is to educate and digitalize the stores in Torsby. From a customer perspective, the platform is a commerce platform. Therefore, they want to be able to see the offers and buy their products. The company perspective is somewhere in between. Some want to be educated and helped to digitalize their business, while others see it more as a tool for selling more products and services. The platform has the potential to help companies develop and change their business models. However, for that to happen, the idea must be more established within the companies. Many of the stores are not ready for such a radical change

Directly observed therapy prior to ambulatory blood pressure measurement (DOT-HTN) in uncontrolled hypertensive patients - Effect on blood pressure, safety and patient perception

Aims: Non-adherence to medication is a key challenge in treatment of hypertensive patients. Directly Observed Therapy prior to ambulatory blood pressure measurement (DOT-HTN) is relatively new in hypertension research and knowledge about its use and patients’ perception of such control is warranted. We aimed to investigate DOT-HTN in relation to blood pressure control, procedural safety and patients’ perception. Methods and results: Twenty patients with uncontrolled hypertension (daytime systolic ambulatory blood pressure measurement (ABPM) ≥135 mm Hg) were randomized to intervention with DOT-HTN and a visual analogue scale (VAS) assessment if they found DOT-HTN problematic (10 cm = very problematic), or to standard ABPM. They were followed for 2–4 weeks. There were no differences in baseline characteristics. Despite no difference in daytime systolic ABPM (p = 0.67) two patients were suggested to be non-adherent after DOT-HTN with reductions in daytime systolic ABPM of 18 and 22 mm Hg, respectively. No post DOT-HTN adverse reactions were reported. VAS assessment indicated that the patients had no problem being controlled (VAS median 0.30 cm (0.0–2.6)), however interesting comments and observed behaviour questioned the reliability of the patient-reported VAS in 38% of patients. Conclusions: Two of eight patients seemed to be non-adherent after DOT-HTN. Descriptive findings suggested reluctance towards control with DOT-HTN not captured by the VAS assessment. No DOT-related medical adverse-effects were reported

Comparison of a single high-sensitivity cardiac troponin T measurement with the HEART score for rapid rule-out of acute myocardial infarction in a primary care emergency setting: a cohort study

Objective This study aims to compare the rule-out safety of a single high-sensitivity cardiac troponin T (hs-cTnT) with the History, ECG, Age, Risk factors and Troponin (HEART) score in a low-prevalence primary care setting of acute myocardial infarction (AMI).Participants Patients with non-specific symptoms suggestive of AMI were consecutively enroled at a primary care emergency clinic in Oslo, Norway from November 2016 to October 2018.Methods After initial assessment by a general practitioner, hs-cTnT samples were drawn. AMI was ruled-out by a single hs-cTnT <5 ng/L measured ≥3 hours after symptom onset. The HEART score was calculated retrospectively; a score ≤3 of 10 points was considered low risk. We also calculated a modified HEART score using more sensitive hs-cTnT thresholds. The primary outcome was the diagnostic performance for the rule-out of AMI at the index event; the secondary the composite of AMI or all-cause death at 90 days.Results Among 1711 patients, 61 (3.6%) were diagnosed with AMI, and 569 (33.3%) patients were assigned to single rule-out (<5 ng/L). With no AMIs in this group, the negative predictive value (NPV) and sensitivity were both 100.0% (95% CI 99.4% to 100.0% and 94.1% to 100.0%, respectively), and the specificity 34.5% (32.2% to 36.8%). The original HEART score triaged more patients as low risk (n=871), but missed five AMIs (NPV 99.4% (98.7% to 99.8%); sensitivity 91.8% (81.9% to 97.3%) and specificity 52.5% (50.0% to 54.9%)). The modified HEART score increased the low-risk sensitivity to 98.4% (91.2% to 100.0%), with specificity 38.7% (36.3% to 41.1%). The 90-day incidence of AMI or death in the single rule-out and the original and modified low-risk HEART groups were 0.0%, 0.7%, and 0.2%, respectively.Conclusion In a primary care emergency setting, a single hs-cTnT strategy was superior to the HEART score in ruling out AMI. This rapid and safe approach may enhance the assessment of patients with chest pain outside of hospitals.Trial registration number NCT02983123