Determinants for use of direct-to-consumer telemedicine consultations in primary healthcare-a registry based total population study from Stockholm, Sweden.

BACKGROUND: In recent years, telemedicine consultations have evolved as a new form of providing primary healthcare. Telemedicine options can provide benefits to patients in terms of access, reduced travel time and no risk of disease spreading. However, concerns have been raised that access is not equally distributed in the population, which could lead to increased inequality in health. The aim of this paper is to explore the determinants for use of direct-to-consumer (DTC) telemedicine consultations in a setting where telemedicine is included in the publicly funded healthcare system. METHODS: To investigate factors associated with the use of DTC telemedicine, a database was constructed by linking national and regional registries covering the entire population of Stockholm, Sweden (N = 2.3 million). Logistic regressions were applied to explore the determinants for utilization in 2018. As comparators, face-to-face physician consultations in primary healthcare were included in the study, as well as digi-physical physician consultations, i.e., telemedicine consultations offered by traditional primary healthcare providers also offering face-to-face visits, and telephone consultations by nurses. RESULTS: The determinants for use of DTC telemedicine differed substantially from face-to-face visits but also to some extent from the other telemedicine options. For the DTC telemedicine consultations, the factors associated with higher probability of utilization were younger age, higher educational attainment, higher income and being born in Sweden. In contrast, the main determinants for use of face-to-face visits were higher age, lower educational background and being born outside of Sweden. CONCLUSION: The use of DTC telemedicine is determined by factors that are generally not associated with greater healthcare need and the distribution raises some concerns about the equity implications. Policy makers aiming to increase the level of telemedicine consultations in healthcare should consider measures to promote access for elderly and individuals born outside of Sweden to ensure that all groups have access to healthcare services according to their needs.

Short- and intermediate-term impact of DTC telemedicine consultations on subsequent healthcare consumption.

AIM: The use of direct-to-consumer (DTC) telemedicine consultations in primary healthcare has increased rapidly, in Sweden and internationally. Such consultations may be a low-cost alternative to face-to-face visits, but there is limited evidence on their effects on overall healthcare consumption. The aim of this study was to assess the short- and intermediate-term impact of DTC telemedicine consultations on subsequent primary healthcare consumption, by comparing DTC telemedicine users to matched controls in a Swedish setting. METHODS: We constructed a database with individual-level data on healthcare consumption, for all residents of Region Stockholm in 2018, by linking national and regional registries. The study population included all individuals who had ≥ 1 physician consultation (telemedicine or face-to-face) during the first half of 2018. DTC telemedicine users were matched 1:2 to controls who were non-users of DTC telemedicine but who had a traditional face-to-face consultation during the study period. The matching criteria were diagnosis and demographic and socioeconomic variables. An interrupted time series analysis was performed to compare the healthcare consumption of DTC telemedicine users to that of the control group. RESULTS: DTC telemedicine users increased their healthcare consumption more than controls. The effect seemed to be mostly short term (within a month), but was also present at the intermediate term (2-6 months after the initial consultation). The results were robust across age and disease groups. CONCLUSION: The results indicate that DTC telemedicine consultations increase the total number of physician consultations in primary healthcare. From a policy perspective, it is therefore important to further investigate for which diagnoses and treatments DTC telemedicine is suitable so that its use can be encouraged when it is most cost-efficient and limited when it is not. Given the fundamentally different models for reimbursement, there are reasons to review and possibly harmonise the incentive structures for DTC telemedicine and traditional primary healthcare.

Simply the best? The impact of quality on choice of primary healthcare provider in Sweden.

OBJECTIVE: One of the more important objectives with the patient choice reform, introducing non-price competition in Swedish primary healthcare, was to improve performance and quality of care. However, in order for choice to lead to quality improvements, citizens need to consider quality aspects in their choices of provider. We hypothesize that quality of care influences choice of provider and the objective of this study is to investigate if citizens are willing to make a trade-off between distance to chosen provider and quality of care. METHODS: We use conditional logit models to analyse if quality and other provider attributes influence choice of provider. The study population includes all citizens of Region Stockholm with at least one primary healthcare contact (N ~1.4 million). RESULTS: The results show that distance is the most important factor in choosing a primary healthcare provider but that there seems to be a willingness to make a trade-off between distance and quality measures. However, other provider attributes, such as the Care Need Index of the registered population, seem to influence choice to a greater extent than quality. CONCLUSION: The results point in the same direction as the arguments behind the patient choice reform. However, the effects are marginal. To enhance quality competition, policy makers should consider making quality information at the provider level more accessible.

Analysis of siRNA specificity on targets with double-nucleotide mismatches.

Although RNA interference as a tool for gene knockdown is a great promise for future applications, the specificity of small interfering RNA (siRNA)-mediated gene silencing needs to be thoroughly investigated. Most research regarding siRNA specificity has involved analysis of affected off-target genes instead of exploring the specificity of the siRNA itself. In this study we have developed an efficient method for generating a siRNA target library by combining a siRNA target validation vector with a nucleotide oligomix. We have used this library to perform an analysis of the silencing effects of a functional siRNA towards its target site with double-nucleotide mismatches. The results indicated that not only the positions of the mismatched base pair have an impact on silencing efficiency but also the identity of the mismatched nucleotide. Our data strengthen earlier observations of widespread siRNA off-target effects and shows that approximately 35% of the double-mutated target sites still causes knockdown efficiency of >50%. We also provide evidence that there may be substantial differences in knockdown efficiency depending on whether the mutations are positioned within the siRNA itself or in the corresponding target site.

Apoptosis resistance downstream of eIF4E: posttranscriptional activation of an anti-apoptotic transcript carrying a consensus hairpin structure.

Aberrant activation of the translation initiation machinery is a common property of malignant cells, and is essential for breast carcinoma cells to manifest a malignant phenotype. How does sustained activation of the rate limiting step in protein synthesis so fundamentally alter a cell? In this report, we test the post transcriptional operon theory as a possible mechanism, employing a model system in which apoptosis resistance is conferred on NIH 3T3 cells by ectopic expression of eIF4E. We show (i) there is a set of 255 transcripts that manifest an increase in translational efficiency during eIF4E-mediated escape from apoptosis; (ii) there is a novel prototype 55 nt RNA consensus hairpin structure that is overrepresented in the 5'-untranslated region of translationally activated transcripts; (iii) the identified consensus hairpin structure is sufficient to target a reporter mRNA for translational activation under pro-apoptotic stress, but only when eIF4E is deregulated; and (iv) that osteopontin, one of the translationally activated transcripts harboring the identified consensus hairpin structure functions as one mediator of the apoptosis resistance seen in our model. Our findings offer genome-wide insights into the mechanism of eIF4E-mediated apoptosis resistance and provide a paradigm for the systematic study of posttranscriptional control in normal biology and disease.

Recording a diagnosis of stroke, transient ischaemic attack or myocardial infarction in primary healthcare and the association with dispensation of secondary preventive medication: a registry-based prospective cohort study.

OBJECTIVES: The aim of this study was to explore whether recording in primary care of a previously recorded hospital diagnosis was associated with increased patient utilisation of recommended medications. DESIGN: Registry-based prospective cohort study. SETTING AND PARTICIPANTS: 19 072 patients with a hospital discharge diagnosis of transient ischaemic attack (TIA), stroke or acute coronary syndrome from hospitals in Stockholm County 2010-2013 were included in the study. MAIN OUTCOME MEASURE: The outcome of the study was medication dispensation as a marker of adherence to recommended medications. Adherence was defined as having had at least two filled prescriptions in the third year following hospital discharge. RESULTS: Recording a diagnosis was associated with higher utilisation of all recommended medications with the exception of antihypertensives in patients with TIA. The differences between the groups with and without a recorded diagnosis remained after adjusting for age, sex, index year and visits to private practitioners. Dispensation of antithrombotics was high overall, 80%-90% in patients without a recorded diagnosis and 90%-94% for those with a diagnosis. Women with recorded ischaemic stroke/TIA/acute coronary syndrome were dispensed more statins (56%-71%) than those with no recorded diagnosis (46%-59%). Similarly, 68%-83% of men with a recorded diagnosis were dispensed statins (57%-77% in men with no recorded diagnosis). The rate of diagnosis recording spanned from 15% to 47% and was especially low in TIA (men 15%, women 16%). CONCLUSION: Recording a diagnosis of TIA/stroke or acute coronary syndrome in primary care was found to be associated with higher dispensation of recommended secondary preventive medications. Further study is necessary in order to determine the mechanisms underlying our results and to establish the utility of our findings.

Antisense-induced Fas mRNA degradation produces site-specific stable 3'-mRNA fragment by exonuclease cleavage at the complementary sequence.

Antisense-mediated degradation of target mRNA is achieved by the enzymatic action of nuclease RNase H. The enzyme recognizes hybrid RNA-DNA duplexes and hydrolyzes the RNA strand. Here, we compared six different phosphorothioate oligonucleotides for their ability to induce target-specific mRNA degradation in cultured mouse AML12 cells. We targeted transcripts of the cell surface receptor Fas and analyzed the levels of mRNA by Northern blotting and ribonuclease protection assay (RPA). Four of the tested antisense oligonucleotides reduced the mRNA levels significantly. Cultures treated with one of the antisense molecules resulted in a shifted band on Northern blots. This band of lower molecular weight was not detected after 6 hours of transfection but appeared at 24 hours. By RPA, the product was shown to be a 3'-cleavage fragment of the full-length Fas mRNA. The RPA also mapped the stable fragment to start within the antisense complementary sequence.

No induction of anti-viral responses in human cell lines HeLa and MCF-7 when transfecting with siRNA or siLNA.

Gene silencing by RNAi and siRNAs has become a well-used tool for researchers. Because of its relatively small size, siRNA was originally thought to avoid activation of anti-viral responses. Recent reports demonstrating so-called "off-target effects" are therefore alarming. One issue raised is that siRNA induces interferon-regulated genes at the transcriptional level. We characterize the anti-viral responses of synthetic siRNA and in vitro-transcribed siRNA by measuring the mRNA levels of IFN-beta and OAS2 in HeLa cells. Transfections with both traditional and LNA-modified synthetic siRNA cause no anti-viral responses, whereas transfection with either long dsRNA or in vitro-transcribed siRNA leads to greater than 1000-fold induction of these genes. The lack of response was also demonstrated at the level of phosphorylated eIF2alpha, and measuring of IFN-beta by ELISA in cell culture media from the human cell line MCF-7. Altogether, transfection with synthetic siRNA does not induce anti-viral responses in these two cell lines. Our results reinforce the role of siRNA as an effective tool for reverse genetics and strengthen siLNA as a tool for future therapeutic applications.

Characterization of RNA interference in rat PC12 cells: requirement of GERp95.

Double-stranded RNA can initiate post transcriptional gene silencing in mammalian cell cultures via a mechanism known as RNA interference (RNAi). The sequence-specific degradation of homologous mRNA is triggered by 21-nucleotide RNA-duplexes termed short interfering RNA (siRNA). The homologous strand of the siRNA guides a multi-protein complex, RNA-induced silencing complex (RISC), to cleave target mRNA. Although the exact function and composition of RISC is still unclear, it has been shown to include several proteins of the Argonaute protein family. Here we report of a robust system to achieve RNAi in a cultured rat neuronal cell line, PC12. Targeting of neuropeptide Y mRNA by synthetic siRNA results in knock down of the mRNA levels with an IC50 of approximately 0.1 nM. The mRNA knockdown lasts for at least 96 h and is not dependent on protein synthesis. Further, PC12 cells were ablated of the rat Golgi-ER protein 95 kDa (GERp95), an Argonaute family protein, by siRNA methodology. After GERp95-ablation, sequential knockdown of NPY by siRNA was shown to be impaired. Thus, we report that the GERp95 protein is functionally required for RNAi targeting NPY in rat PC12 cells.