Abstract
Background
Despite remarkable achievements in antiretroviral therapy (ART), losses to follow-up (LTFU) might prevent the long-term success of HIV treatment and might delay the achievement of ...the 90–90-90 objectives. This scoping review is aimed at the description and analysis of the strategies used in high-income countries to reengage LTFU in HIV care, their implementation and impact.
Methods
A scoping review was done following Arksey & O′Malley’s methodological framework and recommendations from Joanna Briggs Institute. Peer reviewed articles were searched for in Pubmed, Scopus and Web of Science; and grey literature was searched for in Google and other sources of information. Documents were charted according to the information presented on LTFU, the reengagement procedures used in HIV units in high-income countries, published during the last 15 years. In addition, bibliographies of chosen articles were reviewed for additional articles.
Results
Twenty-eight documents were finally included, over 80% of them published in the United States later than 2015. Database searches, phone calls and/or mail contacts were the most common strategies used to locate and track LTFU, while motivational interviews and strengths-based techniques were used most often during reengagement visits. Outcomes like tracing activities efficacy, rates of reengagement and viral load reduction were reported as outcome measures.
Conclusions
This review shows a recent and growing trend in developing and implementing patient reengagement strategies in HIV care. However, most of these strategies have been implemented in the United States and little information is available for other high-income countries. The procedures used to trace and contact LTFU are similar across reviewed studies, but their impact and sustainability are widely different depending on the country studied.
An investigation into the determination of the micromechanical properties of thin film materials has been performed. Thin metal and ceramic films are used extensively in the computer microprocessor ...industry and in the field of micro-electromechanical systems (MEMS). The demand for miniaturization and increased performance has resulted in the use of materials without a clear understanding of their mechanical properties on this scale. Micromechanical properties are difficult to obtain due to the lack of adequate testing equipment. The atomic force microscope (AFM), most commonly used as an imaging tool, lends itself to mechanical interaction with the sample surface utilizing a cantilever probe. An array of aluminum microcantilever beams were fabricated using standard IC processing techniques. The microbeams were deflected by the AFM cantilever probe and from this, the micromechanical properties of stiffness and elastic modulus were determined. Initial results indicate that this technique reliably determines the micromechanical properties of thin films.
Objectives
The aim of the study was to assess the rates of discontinuation of integrase inhibitor regimens because of any neuropsychiatric adverse event (NPAE) and the factors associated with ...discontinuation.
Methods
A population‐based, prospective, multicentre cohort study was carried out. Treatment‐naïve subjects starting therapy with a regimen containing integrase inhibitors, or those switching to such a regimen, with plasma HIV‐1 RNA < 50 HIV‐1 RNA copies/mL in 14 hospitals in Catalonia or the Balearic Islands (Spain) were included in the study. Every discontinuation because of adverse events (AEs) was double‐checked directly with treating physicians. Multivariable Cox models identified factors correlated with discontinuation.
Results
A total of 4165 subjects (37% treatment‐naïve) started regimens containing dolutegravir (n = 1650; 91% with abacavir), raltegravir (n = 930) or elvitegravir/cobicistat (n = 1585). There were no significant differences among regimens in the rate of discontinuation because of any AE. Rates of discontinuation because of NPAEs were low but higher for dolutegravir/abacavir/lamivudine 2.1%; 2.9 (95% confidence interval (CI) 2.0, 4.2) discontinuations/100 patients/year versus elvitegravir/cobicistat (0.5%; 0.8 (95% CI 0.3, 1.5) discontinuations/100 patients/year, with significant differences among centres for dolutegravir/abacavir/lamivudine and NPAEs (P = 0.003). We identified an association of female gender and lower CD4 count with increased risk of discontinuation because of any AE Incidence ratio (IR) 2.3 (95% CI 1.4, 4.0) and 1.8 (95% CI 1.1, 2.8), respectively. Female gender, age > 60 years and abacavir use were not associated with NPAE discontinuations. NPAEs were commonly grade 1–2, and had been present before and improved after drug withdrawal.
Conclusions
In this large prospective cohort study, patients receiving dolutegravir, raltegravir or elvitegravir/cobicistat did not show significant differences in the rate of discontinuation because of any toxicity. The rate of discontinuations because of NPAEs was low, but was significantly higher for dolutegravir than for elvitegravir/cobicistat, with significant differences among centres, suggesting that greater predisposition to believe that a given adverse event is caused by a given drug of some treating physicians might play a role in the discordance seen between cohorts.
In this book, Víctor Ferreres Comella contrasts the European "centralized" constitutional court model, in which one court system is used to adjudicate constitutional questions, with a decentralized ...model, such as that of the United States, in which courts deal with both constitutional and nonconstitutional questions.
Comella's systematic exploration of the reasons for and against the creation of constitutional courts is rich in detail and offers an ambitious theory to justify the European preference for them. Based on extensive research on eighteen European countries, Comella finds that centralized review fits well with the civil law tradition and structures of ordinary adjudication in those countries. Comella concludes that-while the decentralized model works for the United States-there is more than one way to preserve democratic values and that these values are best preserved in the parliamentary democracies of Europe through constitutional courts.
The first years of university can be very challenging for students. Previous research has focused on the study of the prevalence of burnout and of psychological distress in medical students. The aim ...of this study was to investigate the prevalence of psychological symptoms and burnout reported by first-year students, the relationship between these variables and their academic performance, and the differences between health and non-health sciences students.
An observational study with a cross-sectional design was performed. Students of health sciences (medicine, nursing, physiotherapy, psychology), and non-health sciences (biology, social sciences, business management, and engineering) undergraduate programs completed the Brief Symptom Inventory (BSI-18) and the Maslach Burnout Inventory-Student Survey (MBI-SS). Students' grades for the first semester were collected.
A sample of 506 students participated. Prevalence of psychological distress was 27.1% and burnout was 7.3%. Academic performance was unaffected in relation to either psychological distress or burnout. Non-health sciences students showed a greater risk of depression.
This study provides evidence of the high prevalence of psychological distress in the first year of college. Even when burnout prevalence was low, the results suggest the need to introduce prevention programs to improve the psychological wellbeing of these students.
Demyelination and axonal damage are critical processes in the pathogenesis of multiple sclerosis (MS). Oxidative stress and pro-inflammatory cytokines elicited by inflammation mediates tissue damage.
...To monitor the demyelination and axonal injury associated with microglia activation we employed a model using cerebellar organotypic cultures stimulated with lipopolysaccharide (LPS). Microglia activated by LPS released pro-inflammatory cytokines (IL-1β, IL-6 and TNFα), and increased the expression of inducible nitric oxide synthase (iNOS) and production of reactive oxygen species (ROS). This activation was associated with demyelination and axonal damage in cerebellar cultures. Axonal damage, as revealed by the presence of non-phosphorylated neurofilaments, mitochondrial accumulation in axonal spheroids, and axonal transection, was associated with stronger iNOS expression and concomitant increases in ROS. Moreover, we analyzed the contribution of pro-inflammatory cytokines and oxidative stress in demyelination and axonal degeneration using the iNOS inhibitor ethyl pyruvate, a free-scavenger and xanthine oxidase inhibitor allopurinol, as well as via blockage of pro-inflammatory cytokines using a Fc-TNFR1 construct. We found that blocking microglia activation with ethyl pyruvate or allopurinol significantly decreased axonal damage, and to a lesser extent, demyelination. Blocking TNFα significantly decreased demyelination but did not prevented axonal damage. Moreover, the most common therapy for MS, interferon-beta, was used as an example of an immunomodulator compound that can be tested in this model. In vitro, interferon-beta treatment decreased oxidative stress (iNOS and ROS levels) and the release of pro-inflammatory cytokines after LPS stimulation, reducing axonal damage.
The model of neuroinflammation using cerebellar culture stimulated with endotoxin mimicked myelin and axonal damage mediated by the combination of oxidative stress and pro-inflammatory cytokines. This model may both facilitate understanding of the events involved in neuroinflammation and aid in the development of neuroprotective therapies for the treatment of MS and other neurodegenerative diseases.
Oromandibular dystonia (OMD) is an isolated focal dystonia that affects the muscles of the jaw, lower face and tongue. It is a rare disorder but is associated with significant impairment in quality ...of life. Treatment with oral medications has not been successful. Surgical interventions, such as deep brain stimulation, may be of benefit but have not been adequately evaluated. Currently, botulinum toxin (BoNT) injections are regarded as the treatment of choice for OMD. However, the evidence supporting this is not available. Most studies are open label, observational studies, longitudinal clinical experience, case reports or retrospective analysis. From the available studies, OMD is responsive to appropriately targeted BoNT injections. Jaw closing dystonia responds the most robustly. Jaw opening dystonia is more complex to inject, but clinical experience is consistent with benefit. Lingual dystonia is the most difficult because injections into tongue muscles frequently give rise to dysphagia. More controlled studies are required to establish BoNT as an effective treatment for OMD.
•Oromandibular dystonia is an isolated focal dystonia involving the jaw and tongue.•Oral pharmacologic and surgical treatments for oromandibular dystonia are inadequate.•Botulinum toxin is the treatment of choice.•Successful BoNT treatment relies on accurate muscle selection.
This was an international survey undertaken to assess cervical dystonia (CD) patients own perceptions of their illness and its management. A total of 1,071 self-identified respondents with CD in 38 ...countries completed the online survey between March and December 2012. The mean time since diagnosis was 9.6 years and over half (54 %) of patients surveyed were not diagnosed in the first year. When asked how the symptoms of CD affected them, two-thirds (66 %) of patients reported they experienced a lot of pain, and 61 % said that they suffered depression and mood alterations; only 7 % reported no impact on their lives. Despite problems with the diagnosis, almost 70 % of respondents reported being satisfied with the overall relationship with their doctor. Patient treatment expectations were high, with 63 % expecting freedom from spasms and 62 % expecting freedom from pain. Over half (53 %) expected to be able to return to a normal routine (53 %). The most common treatment reported was botulinum toxin (BoNT) (86 %), followed by oral medication (58 %) and physiotherapy/physical therapy (37 %). Among patients treated on BoNT, 56 % were fairly/very satisfied, 25 % were fairly/very dissatisfied and 20 % were neither satisfied nor dissatisfied with the outcome. In conclusion, this international survey highlights the broad impact of CD on several aspects of patient life. Taken overall, the survey suggests that that patients need to be better informed about their condition, treatments available and the limitations of those treatments. It may be that realistically managing patient expectations of treatment would reduce the dissatisfaction of some patients.
To directly compare two serotypes of botulinum toxin (BoNTA and BoNTB) in cervical dystonia (CD) using a randomized, double-blind, parallel-arm study design.
Subjects with CD who had a previous ...response from BoNTA were randomly assigned to BoNTA or BoNTB and evaluated in a blinded fashion at baseline, 4 weeks, 8 weeks, and 2-week intervals thereafter until loss of 80% of clinical effect or completion of 20 weeks of observation. CD severity was measured with the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), and adverse events were assessed by structured interview. Statistical analysis included Wilcoxon rank sum test, log rank tests, and Kaplan-Meier survival curves for duration of effect.
A total of 139 subjects (BoNTA, n = 74; BoNTB, n = 65) were randomized at 19 study sites. Improvement in TWSTRS score was found at 4 weeks after injection and did not differ between serotypes. Dysphagia and dry mouth were more frequent with BoNTB (dysphagia: BoNTA 19% vs BoNTB 48%, p = 0.0005; dry mouth (BoNTA 41% vs BoNTB 80%, p < 0.0001). In clinical responders, BoNT A had a modestly longer duration of benefit (BoNTA 14 weeks, BoNTB 12.1 weeks, p = 0.033).
Both serotypes of botulinum toxin (BoNTA and BoNTB) had equivalent benefit in subjects with cervical dystonia at 4 weeks. BoNTA had fewer adverse events and a marginally longer duration of effect in subjects showing a clinical response.
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