Unsupervised Treatment Research Articles

Effectiveness of artemether-lumefantrine for treating uncomplicated malaria in low- and high-transmission areas of Ghana.

Artemisinin-based combination therapy (ACT) has been effective in the supervised treatment of uncomplicated malaria in Ghana. Since ACT usage is primarily unsupervised, this study aimed to determine the effectiveness of artemether-lumefantrine (AL) for treating malaria patients in two transmission settings in Ghana. Eighty-four individuals with uncomplicated Plasmodium falciparum malaria were recruited from Lekma Hospital (LH) in Accra (low-transmission area; N = 28), southern Ghana, and King's Medical Centre (KMC) in Kumbungu (high-transmission area; N = 56), northern Ghana. Participants were followed up for 28days after unsupervised treatment with AL. The presence of asexual parasites was determined by microscopic examination of Giemsa-stained blood smears. Plasmodium species identification was confirmed using species-specific primers targeting the 18S rRNA gene. Parasite recrudescence or reinfection was determined by genotyping the Pfmsp 1 and Pfmsp 2 genes. After AL treatment, 3.6% (2/56) of the patients from KMC were parasitaemic on day 3 compared to none from the LH patients. One patient from KMC with delayed parasite clearance on day 3 remained parasite-positive by microscopy on day 7 but was parasite-free by day 14. While none of the patients from LH experienced parasite recurrence during the 28-day follow-up, three and two patients from KMC had recurrent parasitaemia on days 21 and 28, respectively. Percentage reduction in parasite densities from day 1, 2, and 3 for participants from the KMC was 63.2%, 89.5%, and 84.5%. Parasite densities for participants from the LH reduced from 98.2%, 99.8% on day 1, and 2 to 100% on day 3. The 28-day cumulative incidence rate of treatment failure for KMC was 12.8% (95% confidence interval: 1.9-23.7%), while the per-protocol effectiveness of AL in KMC was 89.47%. All recurrent cases were assigned to recrudescence after parasite genotyping by Pfmsp 1 and Pfmsp 2. While AL is efficacious in treating uncomplicated malaria in Ghana, when taken under unsupervised conditions, it showed an 89.4% PCR-corrected cure rate in northern Ghana, which is slightly below the WHO-defined threshold.

Safety and tolerability of frozen, capsulized autologous faecal microbiota transplantation. A randomized double blinded phase I clinical trial.

Faecal microbiota transplantation (FMT) is recommended treatment for recurrent Clostridioides difficile infection and is studied as a potential modifier of other gastrointestinal and systemic disorders. Autologous FMT limits the potential risks of donor transplant material and enables prophylactic treatment. Capsulized FMT is convenient and accessible, but safety data are lacking. To describe safety and tolerability of capsules containing autologous FMT, compared to placebo, in healthy volunteers treated with antibiotics. Healthy volunteers without antibiotic exposure during the past three months, that had a negative Clostridioides difficile stool sample, were recruited. Study persons donated faeces for production of capsules containing autologous microbiota. They were then given Clindamycin for seven days to disrupt the intestinal microbiota, which was followed by a two-day washout. Study persons were then randomized (1:1) to unsupervised treatment with autologous faecal matter or placebo, with two capsules twice daily for five days. A standardized questionnaire about side effects and tolerability, daily until day 28, and on days 60 and 180, was completed. Twenty-four study persons were included, all completed the treatment. One person from the placebo and FMT groups each, were lost to follow up from days 21 and 60, respectively. No study person experienced serious side effects, but severe fatigue was reported during the antibiotic period (n = 2). Reported side effects were mild to moderate and there were no significant differences between the groups. Reported general and intestinal health improved significantly and similarly in both groups after the antibiotic treatment. Time to normalized intestinal habits were 17 and 19 days from study start in the placebo group and the FMT group, respectively (p = 0.8). Capsulized frozen autologous faecal microbiota transplantation was safe and well tolerated but did not affect time to normalized intestinal habits compared to placebo. EudraCT 2017-002418-30.

Convexity constraints on linear background models for electron energy-loss spectra

In this paper convexity constraints are derived for a background model of electron energy loss spectra (EELS) that is linear in the fitting parameters. The model outperforms a power-law both on experimental and simulated backgrounds, especially for wide energy ranges, and thus improves elemental quantification results. Owing to the model’s linearity, the constraints can be imposed through fitting by quadratic programming. This has important advantages over conventional nonlinear power-law fitting such as high speed and a guaranteed unique solution without need for initial parameters. As such, the need for user input is significantly reduced, which is essential for unsupervised treatment of large datasets. This is demonstrated on a demanding spectrum image of a semiconductor device sample with a high number of elements over a wide energy range.

The Efficacy and Safety of Etripamil Nasal Spray for Acute Paroxysmal Supraventricular Tachycardia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Paroxysmal supraventricular tachycardia (PSVT) treatment requires medically supervised intervention. Etripamil is a novel short-acting calcium channel blocker. Its intranasal spray formulation has a rapid onset of action and shows promise for the unsupervised treatment of PSVT. We aimed to evaluate the efficacy and safety of etripamil nasal spray for the acute conversion of PSVT. A systematic review and meta-analysis synthesizing randomized controlled trials (RCTs), which were retrieved by systematically searching the PubMed, EMBASE, Web of Science, SCOPUS, and Cochrane databases through to 1 December 2022. RevMan version 5.4 software was used to pool dichotomous outcomes using risk ratio (RR) presented with the corresponding confidence interval (CI). Three RCTs with a total of 496 participants were included in our analysis. Etripamil was effective for PSVT conversion at 15min (RR 1.84, 95% CI 1.37-2.48), 30min (RR 1.86, 95% CI 1.42-2.44), and 60min (RR 1.25, 95% CI 1.05-1.50) after drug administration; decreasing medical intervention-seeking (RR 0.58, 95% CI 0.37-0.90); and decreasing emergency room (ER) visits (RR 0.61, 95% CI 0.38-0.97). However, there was no difference at 300min (RR 1.10, 95% CI 0.97-1.25) and it was associated with higher rates of adverse events (RR 3.17, 95% CI 2.15-4.69). Etripamil nasal spray was effective and well tolerated to induce PSVT termination for up to 60min. Therefore, etripamil nasal spray constitutes a promising strategy for PSVT self-termination without medical supervision; however, further RCTs are required before endorsement in clinical practice.

PO-04-108 THE EFFICACY AND SAFETY OF ETRIPAMIL NASAL SPRAY FOR THE TREATMENT OF ACUTE PAROXYSMAL SUPRAVENTRICULAR TACHYCARDIA: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS

Paroxysmal Supraventricular Tachycardia (PSVT) treatment requires medically supervised intervention. This is derived from the lack of effective and safe self-administrated treatment for PSVT. Etripamil is a novel short-acting calcium channel blocker with a rapid intranasal spray and shows promising potential for the unsupervised treatment of PSVT, especially in the dosage of 70 mg. We aim to evaluate the efficacy and safety of Etripamil for the acute conversion of PSVT. We conducted a systematic review and meta-analysis synthesizing randomized controlled trials (RCTs), which were retrieved by systematically searching: PubMed, EMBASE, Web of Science, SCOPUS, and Cochrane through December 1st, 2022. RevMan version 5.4 software was used to pool dichotomous outcomes using risk ratio (RR) presented with the corresponding confidence interval (CI) while using the fixed-effects model. Three RCTs with a total of 496 patients (296 in the etripamil group and 200 in the placebo group) were included in our analysis. Etripamil was effective for PSVT conversion at 15 minutes (RR: 1.84 with 95% CI [1.37, 2.48]), 30 minutes (RR: 1.86 with 95% CI [1.42, 2.44]), and at 60 minutes after the drug administration (RR: 1.25 with 95% CI [1.05, 1.50]); decreasing medical intervention seeking (RR: 0.58 with 95% CI [0.37, 0.90]); and decreasing emergency (ER) visits (RR: 0.61 with 95% CI [0.38, 0.97]). However, there was no difference at 300 minutes (RR: 1.10 with 95% CI [0.97, 1.25]). Also, Etripamil was associated with higher rates of the incidence of any adverse events (AEs) (RR: 3.17 with 95% CI [2.15, 4.69]), nasal discomfort (RR: 3.82 with 95% CI [2.01, 7.24]), nasal congestion (RR: 5.89 with 95% CI [1.93, 17.97]), epistaxis (RR: 4.74 with 95% CI [1.21, 18.50]), and rhinorrhea (RR: 3.53 with 95% CI [1.22, 10.26]) with no difference regarding any serious adverse events (SAEs) incidence (RR: 0.30 with 95% CI [0.01, 7.21]). Etripamil was effective in inducing PSVT termination for up to 60 minutes and reduced medical treatment seeking and ER visits. Also, Etripamil was associated with higher rates of AEs, including epistaxis, nasal congestion, and rhinorrhea; however, it was not associated with SAEs. Therefore, Etripamil constitutes a promising strategy for PSVT self-termination without medical supervision; however, further RCTs are required before endorsement in clinical practice.

IMPT of head and neck cancer: unsupervised machine learning treatment planning strategy for reducing radiation dermatitis

Radiation dermatitis is a major concern in intensity modulated proton therapy (IMPT) for head and neck cancer (HNC) despite its demonstrated superiority over contemporary photon radiotherapy. In this study, dose surface histogram data extracted from forty-four patients of HNC treated with IMPT was used to predict the normal tissue complication probability (NTCP) of skin. Grades of NTCP-skin were clustered using the K-means clustering unsupervised machine learning (ML) algorithm. A new skin-sparing IMPT (IMPT-SS) planning strategy was developed with three major changes and prospectively implemented in twenty HNC patients. Across skin surfaces exposed from 10 (S10) to 70 (S70) GyRBE, the skin's NTCP demonstrated the strongest associations with S50 and S40 GyRBE (0.95 and 0.94). The increase in the NTCP of skin per unit GyRBE is 0.568 for skin exposed to 50 GyRBE as compared to 0.418 for 40 GyRBE. Three distinct clusters were formed, with 41% of patients in G1, 32% in G2, and 27% in G3. The average (± SD) generalised equivalent uniform dose for G1, G2, and G3 clusters was 26.54 ± 6.75, 38.73 ± 1.80, and 45.67 ± 2.20 GyRBE. The corresponding NTCP (%) were 4.97 ± 5.12, 48.12 ± 12.72 and 87.28 ± 7.73 respectively. In comparison to IMPT, new IMPT-SS plans significantly (P < 0.01) reduced SX GyRBE, gEUD, and associated NTCP-skin while maintaining identical dose volume indices for target and other organs at risk. The mean NTCP-skin value for IMPT-SS was 34% lower than that of IMPT. The dose to skin in patients treated prospectively for HNC was reduced by including gEUD for an acceptable radiation dermatitis determined from the local patient population using an unsupervised MLA in the spot map optimization of a new IMPT planning technique. However, the clinical finding of acute skin toxicity must also be related to the observed reduction in skin dose.

Factors Associated with the Abandonment of Tuberculosis Treatment in Brazil: A Systematic Review.

Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis. In Brazil, TB is a public health problem, and the treatment dropout rate contributes to it. This systematic review investigated the factors associated with TB treatment dropout in Brazil using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method. The databases used were Bireme, Scopus, PubMed, Medline, Pan-American Health Organization (PAHO), and Latin-American and Caribbean Literature on Health Sciences (LILACS). The search was conducted on May 16, 2021. Nine articles were reviewed, and all were published within the last 5 years in English, Spanish, or Portuguese. The sample sizes in the studies ranged from 148 to 77,212 individuals, and the studies enrolled only adult patients (aged 18-59 years) in Brazil. Evidence suggests that the significant risk factors associated with TB treatment dropout are male sex, black race/ethnicity, age between 19 and 49 years, human immunodeficiency virus (HIV) co-infection, low education (<8 years), use of alcohol and illicit drugs, and unsupervised treatment. This study's limitations were the small number of articles published on this topic with stronger study designs, use of secondary data sources in most articles, and a moderate to high risk of bias in most papers. There was a significant association between abandonment of TB treatment and HIV/acquired immunodeficiency syndrome co-infection; socioeconomic factors (low education and homelessness); use of alcohol, tobacco, and illicit drugs; and failure to use directly observed treatment. These results can guide more efficient measures to prevent dropout.

Cost-effectiveness analysis of G6PD diagnostic test for Plasmodium vivax radical cure in Lao PDR: An economic modelling study.

BackgroundPlasmodium vivax (Pv) infections were 68% of the total malaria burden in Laos in 2019. The parasite causes frequent relapses, which can be prevented by primaquine (PMQ). Testing for glucose-6-phosphate-dehydrogenase (G6PD) deficiency is recommended before giving PMQ to avoid haemolysis. Because of the risk of haemolysis in G6PD intermediate deficiencies among females, Laos uses the PMQ 14-days regimen only in G6PD normal females. Among G6PD point-of-care tests, qualitative tests cannot differentiate between G6PD normal and intermediate females. Quantitative tests are required to differentiate between G6PD normal and intermediate deficiencies. However, the quantitative test lacks the cost-effectiveness evidence necessary for decision-making for large-scale adoption. This study examined the cost-effectiveness of quantitative G6PD test, with either supervised PMQ treatment or unsupervised PMQ treatment, against the usual unsupervised PMQ 8-weeks strategy. Supervised PMQ 8-weeks strategy without G6PD testing was also compared against the unsupervised PMQ 8-weeks strategy since the former had recently been adopted in malaria high burden villages that had village malaria volunteers. A budget impact analysis was conducted to understand the incremental cost and effect needed for a nationwide scale-up of the chosen strategy.MethodsA decision tree model compared the cost-effectiveness of implementing four strategies at one health facility with an average of 14 Pv cases in one year. The strategies were unsupervised PMQ strategy, supervised PMQ strategy, G6PD test with unsupervised PMQ strategy, and G6PD test with supervised PMQ strategy. Disability Adjusted Life Years (DALYs) was the effect measure. Costs were calculated from a payer perspective, and sensitivity analyses were conducted. One Gross Domestic Product (GDP) per capita of Laos was set as the cost-effectiveness threshold. Budget impact analysis was conducted using the health facility wise Pv data in Laos in 2020.FindingsSupervised PMQ strategy was extendedly dominated by G6PD test strategies. When compared against the unsupervised PMQ strategy, both G6PD test strategies were more costly but more effective. Their Incremental Cost-Effectiveness Ratios (ICER) were 96.72US$ for the G6PD test with unsupervised PMQ strategy and 184.86US$ for the G6PD test with supervised PMQ strategy. Both ICERs were lower than one GDP per capita in Laos. Following the sensitivity analysis, low adherence for PMQ 14 days made both G6PD test strategies less cost-effective. The lower the Pv case number reported in a health facility, the higher the ICER was. In the budget impact analysis, the expected budget need was only half a million US$ when the G6PD test rollout was discriminately done depending on the Pv case number reported at the health facilities. Indiscriminate roll out of G6PD test to all health facilities was most expensive with least effect impact.

Unsupervised IMU-based evaluation of at-home exercise programmes: a feasibility study

BackgroundThe benefits to be obtained from home-based physical therapy programmes are dependent on the proper execution of physiotherapy exercises during unsupervised treatment. Wearable sensors and appropriate movement-related metrics may be used to determine at-home exercise performance and compliance to a physical therapy program.MethodsA total of thirty healthy volunteers (mean age of 31 years) had their movements captured using wearable inertial measurement units (IMUs), after video recordings of five different exercises with varying levels of complexity were demonstrated to them. Participants were then given wearable sensors to enable a second unsupervised data capture at home. Movement performance between the participants’ recordings was assessed with metrics of movement smoothness, intensity, consistency and control.ResultsIn general, subjects executed all exercises similarly when recording at home and as compared with their performance in the lab. However, participants executed all movements faster compared to the physiotherapist’s demonstrations, indicating the need of a wearable system with user feedback that will set the pace of movement.ConclusionIn light of the Covid-19 pandemic and the imperative transition towards remote consultation and tele-rehabilitation, this work aims to promote new tools and methods for the assessment of adherence to home-based physical therapy programmes. The studied IMU-derived features have shown adequate sensitivity to evaluate home-based programmes in an unsupervised manner. Cost-effective wearables, such as the one presented in this study, can support therapeutic exercises that ought to be performed with appropriate speed, intensity, smoothness and range of motion.

A retrospective analytical study of treatment outcomes among multi drug resistant tuberculosis patients

Background: India is amongst one of the high multidrug resistant tuberculosis (MDR-TB) burden countries globally with a huge contribution given by the state of Uttar Pradesh. Programmatic Management of Drug Resistant Tuberculosis, initiated in 2007 has taken over the disorganized and unsupervised treatment practice in India. However, regular scrutiny is required which points out both its success and failure. Aim &amp; Objective: This study was conducted to evaluate final treatment outcomes among MDR-TB patients on standard Category IV regimen Settings and Design: Retrospective analysis was done using secondary data from medical records of all patients. Methods and Material: Data of all MDR-TB patients registered under RNTCP at King George’s Medical University, Lucknow from 2013 to 2016 was collected. Demographic details along with pre-defined treatment outcomes were recorded (cured, treatment completed, death, treatment failure, treatment default and transfer to higher centre). Statistical analysis used: Descriptive statistics using numbers and percentage. Results: The records of 3580 MDR tuberculosis patients registered at drug resistant tuberculosis centre in King George’s Medical University from January 2013 to December 2016 were included which consisted of 67%males and 33%female. Mean age of presentation was 31.17 years (95% CI 30.75-31.59). Mean weight of patients was 40.16 kg (95% CI 39.89-40.43). Year wise distribution of registered cases from 2013 to 2016 was 611, 799, 984 and 1186 patients respectively. Amongst 3580 patients, 30.39% were declared cured, 25.50% completed treatment, 21.39% died, 0.84% showed treatment failure, 12.54% were defaulters, 2.35% were transferred out to higher centre, 6.5% were shifted to regimen for Extensive drug resistant (EDR) TB, 0.16% patients needed to stop treatment due to ADR and 0.33% patient were still on treatment. Conclusion: The treatment success rate of MDR?TB patients is still low. Measures to improve treatment adherence as in National tuberculosis elimination programme (NTEP) attempts to further improve the success rate.

Supervised versus unsupervised primaquine radical cure for the treatment of falciparum and vivax malaria in Papua, Indonesia: a cluster-randomised, controlled, open-label superiority trial

SummaryBackgroundThere is a high risk of Plasmodium vivax recurrence in patients treated for Plasmodium falciparum malaria in co-endemic areas. Primaquine radical cure has the potential to reduce P vivax recurrences in patients presenting with P falciparum as well as P vivax malaria but is undermined by poor adherence to the currently recommended 14-day regimen. We aimed to assess the efficacy and safety of supervised versus unsupervised primaquine radical cure in patients presenting with uncomplicated malaria.MethodsWe did a cluster-randomised, controlled, open-label superiority trial in Papua, Indonesia. 21 clusters of village health posts, matched by annual parasite index, were randomly assigned (1:1) to treat patients (age >12 months and body weight >5 kg) presenting with confirmed uncomplicated P falciparum or P vivax malaria with oral dihydroartemisinin–piperaquine plus either a supervised or unsupervised 14-day course of oral primaquine (0·5 mg/kg per day). Patients in the supervised group were supervised taking their primaquine dose on alternate days. Patients were followed-up for 6 months and those who presented again with malaria were retreated with the same drug regimen. Masking was not possible due to the nature of the study. The primary outcome was the incidence risk of P vivax malaria over 6 months, assessed in the modified intention-to-treat population (all patients who were assigned to a treatment group, excluding patients who were lost to follow-up after their first visit). This trial is now complete, and is registered with ClinicalTrials.gov, NCT02787070.FindingsBetween Sept 14, 2016, and July 31, 2018, 436 patients were screened for eligibility and 419 were enrolled; 223 (53%) patients in 11 clusters were assigned to supervised primaquine treatment and 196 (47%) in ten clusters to unsupervised primaquine treatment. 161 (72%) of 223 patients in the supervised group and 151 (77%) of 196 in the unsupervised group completed 6 months of follow-up. At 6 months, the incidence risk of P vivax recurrence in the supervised group was 29·7% (95% CI 16·4–49·9) versus 55·8% (32·3–81·8) in the unsupervised group (hazard ratio 0·23 [95% CI 0·07–0·76]; p=0·016). The incidence rate for P vivax recurrence was 539 (95% CI 390–747) infections per 1000 person-years in the supervised group versus 859 (673–1096) in the unsupervised group (incidence rate ratio 0·63 [95% CI 0·42–0·94]; p=0·025). The corresponding rates in the 224 patients who presented with P falciparum malaria were 346 (95% CI 213–563) and 660 (446–977; incidence rate ratio 0·52 [95% CI 0·28–0·98]; p=0·043). Seven serious adverse events were reported (three in the supervised group, four in the unsupervised group), none of which were deemed treatment-related, and there were no deaths.InterpretationIn this area of moderate malaria transmission, supervision of primaquine radical cure treatment reduced the risk of P vivax recurrence. This finding was apparent for patients presenting with either P falciparum or P vivax malaria. Further studies are warranted to investigate the safety and efficacy of radical cure for patients presenting with uncomplicated falciparum malaria in other co-endemic areas.FundingThe Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Foreign Affairs and Trade of the Australian Government.TranslationFor the Indonesian translation of the abstract see Supplementary Materials section.

Revealing Contamination and Sequence of Overlapping Fingerprints by Unsupervised Treatment of a Hyperspectral Secondary Ion Mass Spectrometry Dataset.

Time-of-flight secondary ion mass spectrometry (ToF-SIMS) has been successfully applied for chemical imaging of overlapping fingermarks. The resulting big dataset has been treated by means of an unsupervised machine learning approach based on uniform manifold approximation and projection. The hyperspectral matrix was composed of 49 million pixels associated with 518 peaks. However, the single-pixel spectrum results in a very poor signal intensity, mostly like a barcode. Contrary to what has been reported in the literature recently, we have not applied a crude approach based on binning but a sophisticated machine learning method capable of separating the chemical signals of the two fingerprints from each other and from the substrate in which they were impressed. Moreover, using ToF-SIMS, an extremely surface-sensitive technique, the sequence of deposition of the fingerprints has been determined.

Evaluation of the effect of supervised anti-malarial treatment on recurrences of Plasmodium vivax malaria

BackgroundRelapses in vivax malaria have posed great challenges for malaria control, and they also account for a great proportion of reported cases. Knowing the real effectiveness of a 7-day primaquine (PQ) scheme is crucial in order to evaluate not only the cost-effectiveness of implementing new anti-hypnozoite drugs, but also how health education strategies can guarantee better compliance and be reinforced. This study aimed to evaluate the effect of daily treatment with chloroquine and PQ supervised by health workers versus prescription without supervision.MethodsThe outcome was the passive detection of new positive thick blood smears up to 180 days, based on the official data records from the National Malaria Control Programme. The recurrences seen in the real life were, therefore, used as a surrogate for true relapses.ResultsPatients under supervised treatment had a lower risk of recurrence up to day 180 when compared to the unsupervised treatment (17.9% vs. 36.1%; p = 0.027).ConclusionsThe lack of supervision in the non-supervised group (which followed standard of care in the real life) enabled proper comparison, as consent itself would have lead to greater compliance in this group. Future studies should scale such an analysis to different settings in the Brazilian Amazon.

Global economic costs due to vivax malaria and the potential impact of its radical cure: A modelling study.

In 2017, an estimated 14 million cases of Plasmodium vivax malaria were reported from Asia, Central and South America, and the Horn of Africa. The clinical burden of vivax malaria is largely driven by its ability to form dormant liver stages (hypnozoites) that can reactivate to cause recurrent episodes of malaria. Elimination of both the blood and liver stages of the parasites ("radical cure") is required to achieve a sustained clinical response and prevent ongoing transmission of the parasite. Novel treatment options and point-of-care diagnostics are now available to ensure that radical cure can be administered safely and effectively. We quantified the global economic cost of vivax malaria and estimated the potential cost benefit of a policy of radical cure after testing patients for glucose-6-phosphate dehydrogenase (G6PD) deficiency. Estimates of the healthcare provider and household costs due to vivax malaria were collated and combined with national case estimates for 44 endemic countries in 2017. These provider and household costs were compared with those that would be incurred under 2 scenarios for radical cure following G6PD screening: (1) complete adherence following daily supervised primaquine therapy and (2) unsupervised treatment with an assumed 40% effectiveness. A probabilistic sensitivity analysis generated credible intervals (CrIs) for the estimates. Globally, the annual cost of vivax malaria was US$359 million (95% CrI: US$222 to 563 million), attributable to 14.2 million cases of vivax malaria in 2017. From a societal perspective, adopting a policy of G6PD deficiency screening and supervision of primaquine to all eligible patients would prevent 6.1 million cases and reduce the global cost of vivax malaria to US$266 million (95% CrI: US$161 to 415 million), although healthcare provider costs would increase by US$39 million. If perfect adherence could be achieved with a single visit, then the global cost would fall further to US$225 million, equivalent to $135 million in cost savings from the baseline global costs. A policy of unsupervised primaquine reduced the cost to US$342 million (95% CrI: US$209 to 532 million) while preventing 2.1 million cases. Limitations of the study include partial availability of country-level cost data and parameter uncertainty for the proportion of patients prescribed primaquine, patient adherence to a full course of primaquine, and effectiveness of primaquine when unsupervised. Our modelling study highlights a substantial global economic burden of vivax malaria that could be reduced through investment in safe and effective radical cure achieved by routine screening for G6PD deficiency and supervision of treatment. Novel, low-cost interventions for improving adherence to primaquine to ensure effective radical cure and widespread access to screening for G6PD deficiency will be critical to achieving the timely global elimination of P. vivax.

The clinical effects of mobilization with passive ankle dorsiflexion using a passive ankle dorsiflexion apparatus on older patients with knee osteoarthritis: A randomized trial.

Active exercise is the only proven effective intervention for knee osteoarthritis (OA). The addition of manual therapy has shown to improve outcome of exercises. Passive mobilization with submaximal bilateral passive ankle dorsiflexion was examined in a double-blinded randomized controlled clinical trial. A passive ankle dorsiflexion apparatus was used to standardize the frequency, range of motion, and duration parameters. The purpose of the study was to determine whether a simple standardised mobilization technique could be incorporated as a safe and unsupervised conservative treatment for knee OA. In total, 73 participants were randomly assigned to the experimental (n= 37) or control group (n= 36). All participants performed active exercises and received six sessions of 10-minute dorsiflexion intervention, either real or sham, for two weeks. Pre- and post-experimental assessments for the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), visual analog scale (VAS) for pain, and range of motion of the knee were conducted. Results were analyzed using two-way repeated measures analysis of variance and Independent-Samples Mann-Whitney U Test. The mean score of WOMAC for the experimental and control groups changed from 31.84 to 18.19 and 34.74 to 21.06, respectively, after the intervention. The VAS also showed significant improvements. Significant improvements were observed in WOMAC in both groups after the intervention; however, differences between the groups were not statistically significant. Exercise with either 30∘ or 5∘ of passive dorsiflexion yielded favorable clinical effects. Although submaximal bilateral ankle dorsiflexion was proven to be safe for elderly participants with osteoarthritis of the knee, whether it provided extra benefits to exercises alone was unclear. Further research is required to determine the effectiveness of dorsiflexion and optimal range of mobilization.

First experience of autonomous, un-supervised treatment planning integrated in adaptive MR-guided radiotherapy and delivered to a patient with prostate cancer

Background and purposeCurrently clinical radiotherapy (RT) planning consists of a multi-step routine procedure requiring human interaction which often results in a time-consuming and fragmented process with limited robustness. Here we present an autonomous un-supervised treatment planning approach, integrated as basis for online adaptive magnetic resonance guided RT (MRgRT), which was delivered to a prostate cancer patient as a first-in-human experience. Materials and methodsFor an intermediate risk prostate cancer patient OARs and targets were automatically segmented using a deep learning-based software and logical volume operators. A baseline plan for the 1.5 T MR-Linac (20x3 Gy) was automatically generated using particle swarm optimization (PSO) without any human interaction. Plan quality was evaluated by predefined dosimetric criteria including appropriate tolerances. Online plan adaptation during clinical MRgRT was defined as first checkpoint for human interaction. ResultsOARs and targets were successfully segmented (3 min) and used for automatic plan optimization (300 min). The autonomous generated plan satisfied 12/16 dosimetric criteria, however all remained within tolerance. Without prior human validation, this baseline plan was successfully used during online MRgRT plan adaptation, where 14/16 criteria were fulfilled. As postulated, human interaction was necessary only during plan adaptation. ConclusionAutonomous, un-supervised data preparation and treatment planning was first-in-human shown to be feasible for adaptive MRgRT and successfully applied. The checkpoint for first human intervention was at the time of online MRgRT plan adaptation. Autonomous planning reduced the time delay between simulation and start of RT and may thus allow for real-time MRgRT applications in the future.

COVID-ified’ orthodontic practice: A review

Corona virus disease 2019 (COVID-19) is a contagious disease caused by severe acute respiratory syndrome corona virus (SARS-CoV-2). It emerged as a global pandemic in early 2020, affecting more than 200 countries and territories. As SARS-CoV-2 has also been identified in the saliva of infected individuals, it poses a significant risk for dental professionals and their patients. This article focuses on the changes which are to stay in the wake of COVID-19 especially with respect to orthodontic practice. It is important to have a thorough knowledge about handling the procedures and emergencies in the current scenario or in the wake of an unprecedented future lockdown. Practitioners must anticipate and be prepared for the effects of unsupervised orthodontic treatment in the wake of unprecedented suspension of elective treatment due to COVID 19. This literature also focuses on publications regarding this new corona virus and supplies valuable indications to professionals concerning protective and preventive measures that can be adopted.Orthodontically relevant sources of information were searched using electronic databases including PubMed and Google Scholar, Scopus and SciELO. As keywords, the terms “Orthodontics” and “Covid-19” were used in English. Where available, peer-reviewed and more recent publications were given priority.

Effect of varenicline directly observed therapy versus varenicline self-administered therapy on varenicline adherence and smoking cessation in methadone-maintained smokers: a randomized controlled trial.

Level of adherence to tobacco cessation medication regimens is believed to be causally related to medication effectiveness. This study aimed to evaluate the efficacy of varenicline directly observed therapy (DOT) on varenicline adherence and smoking cessation rates among smokers with opioid use disorder (OUD) receiving methadone treatment. Multicenter, parallel-group two-arm randomized controlled trial. Urban opioid treatment program (OTP) in the Bronx, New York, USA. Daily smokers of ≥5 cigarettes/day, interested in quitting (ladder of change score 6-8), in methadone treatment for ≥3months, attending OTP≥3days/week. Participants' mean age was 49years, 56% were male, 44% Latino, 30% Black, and they smoked a median of 10 cigarettes/day. Individual, block, random assignment to 12weeks of varenicline, either directly observed with methadone (DOT, n=50) or via unsupervised self-administered treatment (SAT, n=50). The primary outcome was adherence measured by pill count. The secondary outcome was 7-day point prevalence tobacco abstinence verified by expired carbon monoxide (CO)<8 parts per million. Retention at 24weeks was 92%. Mean adherence was 78.5% [95% confidence interval (CI)=71.8-85.2%] in the DOT group versus 61.8% in the SAT group (95% CI=55.0-68.6%); differences were driven by DOT effects in the first 6weeks. CO-verified abstinence did not differ between groups during the intervention (P=0.26), but was higher in the DOT than the SAT group at intervention end (DOT=18% versus SAT=10%, difference=8%, 95% CI=-13, 28); this difference was not significant (P=0.39) and was not sustained at 24-week follow-up. Among daily smokers attending opioid treatment programs, opioid treatment program-based varenicline directly observed therapy was associated with early increases in varenicline adherence compared with self-administered treatment, but findings were inconclusive as to whether directly observed therapy was associated with a difference in tobacco abstinence.

Advantages of Outpatient Treatment with Long-Acting Lipoglycopeptides for Serious Gram-Positive Infections: A Review.

Treatment of serious gram-positive infections presents multiple challenges. Treatment often results in prolonged hospitalization for administration of intravenous antimicrobials and presents an inefficient use of hospital resources. Prolonged hospitalization is typically also unfavorable to patient preferences and potentially subjects patients to additional health care-associated complications. Current strategies of transition to outpatient settings-outpatient parenteral antimicrobial therapy and use of oral antibiotics-often do not adequately serve vulnerable populations for whom there is often no alternative to inpatient therapy. Specifically, people who use drugs, those who cannot reliably adhere to unsupervised treatment (poor mental or physical health), people with complicating life circumstances (e.g., homelessness, incarceration, rural location), and those with inadequate health insurance remain hospitalized for weeks longer than persons without such conditions. We suspected that long-acting lipoglycopeptides (laLGP), such as dalbavancin and oritavancin, may be useful in patient transitions to outpatient settings. Thus, we conducted a search of the peer-reviewed literature using the PubMed, Google Scholar, and MEDLINE databases. Based on accumulating literature, it appears that laLGPs offer a reliable alternative therapeutic strategy that addresses many of the personal and systemic barriers to the traditional transitioning approaches. Current evidence also suggests that these agents may be cost-effective from patient, payer, and hospital perspectives. Barriers to broader use of laLGPs include, among others, a relative lack of prospective data regarding efficacy in serious infections, a narrow United States Food and Drug Administration-approved indication restricted to only acute bacterial skin and skin structure infections, and lack of reimbursement infrastructure for inpatient settings.

Early results of supervised versus unsupervised rehabilitation of patients with cervical pain.

Comparison of early effects of supervised (led by physiotherapist) and unsupervised rehabilitation protocols in patients with myofascial pain syndrome, disk-root conflict and degenerative spine disease at cervical level. Three groups of patients (n = 60 each) with clinically and neurophysiologically confirmed myofascial pain syndrome, disk-root conflict and degenerative spine disease were randomly subdivided to supervised and unsupervised treatment subgroups (n = 30 each). Thirty healthy subjects with similar demographic and anthropometric properties as patients were enrolled to control group. Patients were examined before and after rehabilitation with visual analog scale of pain, Spurling's test, painful passive elongation and active trigger points detection in trapezius muscle, sensory perception studies and surface electromyography (at rest, during maximal contraction) and electroneurography. Supervised treatment resulted in decrease of pain intensity (P = .001) and Spurling's symptoms incidence (P = .008) in patients from disk-root conflict group. Painful elongation and incidence of trigger points in trapezius muscle were the least observed at P = .009 after supervised therapy of myofascial pain syndrome. Supervised therapy resulted in decrease of resting electromyography amplitude and increase of maximal contraction electromyography amplitude from trapezius muscle (P = .02) in myofascial pain syndrome patients and from biceps and abductor pollicis brevis muscles of patients from other groups (P from .05 to .001). Median nerve electroneurography and sensory perception results improved at P = .05 after supervised treatment in disk-root conflict group. Twenty-day supervised rehabilitation provides better therapeutic effects than unsupervised one in treatment of muscle dysfunctions in patients with myofascial pain syndrome, degenerative changes and disk-root conflict at cervical spine.