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ZusammenfassungLokale Wundinfektionen sind ein multidisziplinär relevantes Problem und sollten möglichst frühzeitig diagnostiziert und adäquat therapiert werden. Neben einer Stagnation der Wundheilung sind es insbesondere die drohende Weiterentwicklung zu systemischen Infektionen bis hin zur Sepsis, die gefürchtete, potenziell lebensbedrohliche Komplikationen darstellen. Einen besonders hohen und multidisziplinären Stellenwert hat diese Thematik bei der Behandlung von Patienten mit chronischen Wunden. Bislang gab es für die Diagnostik keine einheitlich akzeptierten Kriterien. Hier ermöglicht jetzt der neu entwickelte und validierte TILI-Score als Ergänzung zu den Vitalparametern und serologischen Werten die rasche Objektivierung lokaler Wundinfektionen. Ergänzend können mit dem W.A.R.-Score zudem Patienten mit erhöhtem Infektionsrisiko identifiziert werden. Durch diese einfach einzusetzenden Hilfsmittel kann die Indikation einer antiseptischen Wundtherapie individuell, schnell und unproblematisch eingeschätzt werden. Für viele Patienten mit chronischen Wunden ist dann Polihexanid das Wundantiseptikum der ersten Wahl. Die Indikation von Wundantiseptika sollte aber spätestens nach einer Therapiedauer von 14 Tagen kritisch überprüft werden.

Objective The aim of this study was to examine the effectiveness of a real-world, population-scaled, school-based physical activity (PA) intervention that provided two to three additional physical education lessons per week to children aged 6 to 14 years in Slovenia. Methods More than 34,000 participants from over 200 schools were compared with a similar number of nonparticipants from the same schools. Generalized estimating equations were used to estimate the effects of differing levels of exposure to the intervention (i.e., from 1–5 years) on BMI in children with normal weight, overweight, or obesity at baseline. Results BMI was lower in the intervention group, irrespective of participation duration or baseline weight status. The difference in BMI increased with the program duration, with maximal effects being seen after 3 to 4 years of participation, and was consistently larger for children with obesity (peaking at 1.4 kg/m2 [95% CI: 1.0–1.9] for girls with obesity and peaking at 0.9 kg/m2 [95% CI: 0.6–1.3] for boys with obesity). The program started to become effective at reversing obesity after 3 years, whereas the lowest numbers needed to treat (NNTs) were observed after 5 years (NNTs = 17 for girls and 12 for boys). Conclusions The population-scaled, school-based PA intervention was effective in preventing and treating obesity. The effects were the greatest in children initially presenting with obesity, such that the program was able to benefit children needing support the most.

Introduction The use of aligner therapy for orthodontic treatment has increased substantially in the past decade. However, no study has compared treatment outcomes between the conventional fixed appliance and Invisalign therapies in patients with a severe deep overbite. Methods This study included 50 consecutive adult patients who underwent treatment with either Invisalign (n = 25; mean age, 23.3 ± 8.5 years) or a conventional fixed appliance (n = 25; mean age, 23.1 ± 6.5 years) to correct overbite >5 mm and >60% deep overbite. Cephalometric analysis and peer assessment rating was used to compare the clinical outcome between groups. Results Cephalometric analysis showed significant differences in N-Me (P = 0.0005) and Mp-L6 (P = 0.0001) between Invisalign and fixed appliance treatment groups. No significant differences were observed in the peer assessment rating analysis or total treatment duration between the 2 groups. Conclusions Both Invisalign and conventional fixed appliances were effective in treating patients with a severe deep overbite. Invisalign therapy may be preferable over conventional fixed appliance therapy in patients with high angle and deep overbite. However, because this study had a retrospective design, the results should be viewed with caution.

Cold Atmospheric Plasma (CAP) jet is an ionized gas with a rich combination of reactive oxygen/nitrogen species, charged particles, and photons. By both in vitro and in vivo experiments, it has been demonstrated that CAP can be successfully utilized in cancer treatments. However, the therapeutic effects of CAP depend on various factors such as plasma discharge voltage, gas composition, treatment duration, and type of cancer cells. This paper presents an adaptive plasma system, where the CAP treatment conditions are adjusted online depending on the actual cancer cell response. In particular, we utilize safe Q-learning to schedule CAP cancer treatment autonomously while prohibiting excessive treatments caused by large uncertainties. As it is capable of learning the dynamic characteristics of the particular cancer cell under treatments in situ, we can treat cancer successfully without the complete prior knowledge of cancer characteristics, where the uncertainties of the learned dynamics are carefully accounted. The efficacy of the proposed algorithm is illustrated by numerical examples with an empirical cancer dynamic model constructed from in vitro experiments.

Neonatal meningitis can be devastating for the developing brain. Over decades, mortality has been reduced with better diagnostic modalities and early use of antibiotics. However, the long-term outcome is still poor for many babies. Pathogens causing meningitis include the most common bacteria to some rare viral or fungal entities. Early suspicion and prompt treatment are our best weapons against this old enemy. Treatment duration varies depending upon the pathogen and clinical response. Neuroimaging plays an important role in prognosis and MRI brain is emerging as an excellent outcome predictor. Prevention or very early treatment, by implementing holistic care to neonates and pregnant mothers and identifying the risk factors as early as possible, is essential to improve outcomes. This short article provides an overview of neonatal meningitis and discusses the recommendations for diagnosis and treatment offered in some of the evidence-based clinical practice guidelines used in higher income countries.

Introduction This retrospective study aimed to evaluate whether there are differences in the duration of treatment and the quality of treatment results between patients whose entire treatment process is carried out by a single operator and those patients who are transferred to a second operator. Methods One hundred twenty-three patients whose fixed orthodontic treatments were completed and included in the study, and their posttreatment plaster models and panoramic radiographs were used. Fifty-nine of the subjects were transfer patients, and their treatment was administered by 2 residents (transfer group). For the remaining 64 patients, all the treatment was carried out by a single resident (control group). Each group was further divided into 2 groups according to the treatment modality, resulting in 4 groups (nonextraction transfer group [n = 27], extraction transfer group [n = 32], nonextraction control group [n = 32], and extraction control group [n = 32]). The quality of the treatment outcomes was evaluated and compared using the American Board of Orthodontics cast-radiograph evaluation (CRE). Results The total mean CRE scores in the nonextraction transfer and nonextraction control groups were 35.74 and 29.88, respectively. The means of treatment duration in the nonextraction transfer and nonextraction control groups were 32.7 months and 17.25 months, respectively. The total mean CRE scores in the extraction transfer and extraction control groups were 39.53 and 31.41, respectively. The means of treatment duration in the extraction transfer and extraction control groups were 34.38 and 22.94 months, respectively. Differences between all the compared pairings were statistically significant. Conclusions The transferred patients had longer treatment times and poorer treatment quality than the control group patients.

Brain imaging techniques enable the visualization of serotonin transporter (SERT) occupancy as a measure of the proportion of SERT blocked by an antidepressant at a given dose. We aimed to systematically review the evidence on the relationship between antidepressant dose and SERT occupancy. We searched PubMed and Embase (last search 20 May 2021) for human in vivo, within-subject PET, or SPECT studies measuring SERT occupancy at any dose of any antidepressant with highly selective radioligands ([11C]-DASB, [123I]-ADAM, and [11C]-MADAM). We summarized and visualized the dose-occupancy relationship for antidepressants across studies, overlaying the plots with a curve based on predicted values of a standard 2-parameter Michaelis–Menten model fitted using the observed data. We included seventeen studies of 10 different SSRIs, SNRIs, and serotonin modulators comprising a total of 294 participants, involving 309 unique occupancy measures. Overall, following the Michaelis–Menten equation, SERT occupancy increased with a higher dose in a hyperbolic relationship, with occupancy increasing rapidly at lower doses and reaching a plateau at approximately 80% at the usual minimum recommended dose. All the studies were small, only a few investigated the same antidepressant, dose, and brain region, and few reported information on factors that may influence SERT occupancy. The hyperbolic dose-occupancy relationship may provide mechanistic insight of relevance to the limited clinical benefit of dose-escalation in antidepressant treatment and the potential emergence of withdrawal symptoms. The evidence is limited by non-transparent reporting, lack of standardized methods, small sample sizes, and short treatment duration. Future studies should standardize the imaging and reporting procedures, measure occupancy at lower antidepressant doses, and investigate the moderators of the dose-occupancy relationship.

Summary Context The administration of immune checkpoints inhibitors (ICIs) within hospitalization at home (HaH) organizations is an interesting alternative to conventional care. Three surveys were carried out to describe the different organizational models of French HaHs and criteria used by physicians in patient selection. Methods Three surveys were conducted between April 1 and August 31, 2020. The first one was addressed to all French HaHs, and the two others to public HaHs and oncologists treating patients with solid cancer in the Auvergne-Rhone-Alpes region. Results Overall, 54 French HaHs and 23 oncologists participated to the study. The health professionals involved in the patients’ care were very heterogeneous, although in 92% of cases, the treatment prescription was made by the oncologist. HaH physicians were more involved in clinical assessment the day before treatment (19% vs. 0%), treatment validation (56% vs. 15%), and treatment prescription (19% vs. 0%), while nurses were better equipped (emergency kit available in 81% versus 50% of cases) when HaHs did carry out ICIs compared to when they did not. Most oncologists agreed that age, neuropsychiatric disorders, home environment, as well as treatment duration and good tolerance should be considered in patient selection. ECOG PS status and treatment response were less consensually considered. Conclusion These results highlight the variability in French HaH organizations and patient selection criteria for employing ICIs at home. This study resulted in recommendations for administrating ICIs in HaH settings, which will likely be instrumental in further promoting this activity across France.

BackgroundIn the previously reported SAPS trial (https://clinicaltrials.gov/ct2/show/NCT01139489), procalcitonin-guidance safely reduced the duration of antibiotic treatment in critically ill patients. We assessed the impact of shorter antibiotic treatment on antimicrobial resistance development in SAPS patients.Materials and methodsCultures were assessed for the presence of multi-drug resistant (MDR) or highly resistant organisms (HRMO) and compared between PCT-guided and control patients. Baseline isolates from 30 days before to 5 days after randomization were compared with those from 5 to 30 days post-randomization. The primary endpoint was the incidence of new MDR/HRMO positive patients.ResultsIn total, 8,113 cultures with 96,515 antibiotic test results were evaluated for 439 and 482 patients randomized to the PCT and control groups, respectively. Disease severity at admission was similar for both groups. Median (IQR) durations of the first course of antibiotics were 6 days (4–10) and 7 days (5–11), respectively (p = 0.0001). Antibiotic-free days were 7 days (IQR 0–14) and 6 days (0–13; p = 0.05). Of all isolates assessed, 13% were MDR/HRMO positive and at baseline 186 (20%) patients were MDR/HMRO-positive. The incidence of new MDR/HRMO was 39 (8.9%) and 45 (9.3%) in PCT and control patients, respectively (p = 0.82). The time courses for MDR/HRMO development were also similar for both groups (p = 0.33).ConclusionsIn the 921 randomized patients studied, the small but statistically significant reduction in antibiotic treatment in the PCT-group did not translate into a detectable change in antimicrobial resistance. Studies with larger differences in antibiotic treatment duration, larger study populations or populations with higher MDR/HRMO incidences might detect such differences.

[Background] We aim to compare the effect of short versus long treatment duration in Gram-negative bacteremia on all-cause mortality in pre-specified sub-groups., [Methods] Individual participant data meta-analysis of randomized controlled trials (RCTs) comparing short (≤7) versus longer (>7 days) antibiotic treatment for Gram-negative bacteremia. Participants were adults (≥18 years), with Gram-negative bacteremia during hospital stay. We searched PubMed, Cochrane Central Register of Controlled Trials, and Web of Science to identify trials conducted up to May 2022. Primary outcome was 90-day all-cause mortality. Secondary outcomes were 30-day mortality, relapse of bacteremia, length of hospital stay, readmission, local or distant infection complications, adverse events, and resistance emergence. Outcomes were assessed in pre-specified subgroups: women vs men; non-urinary vs urinary source; presence vs absence of hypotension on initial presentation; immunocompromised patients versus non-immunocompromised patients, and age (above/below 65). Fixed-effect meta-analysis model was used to estimate pooled odds ratio (OR) and 95% confidence interval (CI). All three trials had low risk of bias for allocation generation and concealment., [Findings] Three RCTs (1186 patients) were included; 1121 with enterobacterales bacteremia. No significant difference in mortality was demonstrated between 7- and 14-days treatment (90-day mortality: OR 1.08, 95% CI 0.73–1.58; 30-day mortality: 1.08, 0.62–1.91). Relapse (1.00, 0.50–1.97); length of hospital stay (P = 0.78); readmission (0.96, 0.80–1.22); and infection complications (local: 1.62 0.76–3.47; distant: 2.00, 0.18–22.08), were without significant difference, and so were adverse events or resistance emergence. No significant difference in clinical outcomes between 7 and 14 days of antibiotics was demonstrated in the subgroups of gender, age, hemodynamic status, immune status, and source of infection., [Interpretation] For patients hemodynamically stable and afebrile at 48 h prior to discontinuation, seven days of antibiotic therapy for enterobacterales bacteremia result in similar outcomes as 14 days, in terms of mortality, relapse, length of hospital stay, complications of infection, resistance emergence, and adverse events. These results apply for any adult age group, gender, source of infection, immune status, and hemodynamic status on presentation.

Background We aim to compare the effect of short versus long treatment duration in Gram-negative bacteremia on all-cause mortality in pre-specified sub-groups. Methods Individual participant data meta-analysis of randomized controlled trials (RCTs) comparing short (≤7) versus longer (>7 days) antibiotic treatment for Gram-negative bacteremia. Participants were adults (≥18 years), with Gram-negative bacteremia during hospital stay. We searched PubMed, Cochrane Central Register of Controlled Trials, and Web of Science to identify trials conducted up to May 2022. Primary outcome was 90-day all-cause mortality. Secondary outcomes were 30-day mortality, relapse of bacteremia, length of hospital stay, readmission, local or distant infection complications, adverse events, and resistance emergence. Outcomes were assessed in pre-specified subgroups: women vs men; non-urinary vs urinary source; presence vs absence of hypotension on initial presentation; immunocompromised patients versus non-immunocompromised patients, and age (above/below 65). Fixed-effect meta-analysis model was used to estimate pooled odds ratio (OR) and 95% confidence interval (CI). All three trials had low risk of bias for allocation generation and concealment. Findings Three RCTs (1186 patients) were included; 1121 with enterobacterales bacteremia. No significant difference in mortality was demonstrated between 7- and 14-days treatment (90-day mortality: OR 1.08, 95% CI 0.73–1.58; 30-day mortality: 1.08, 0.62–1.91). Relapse (1.00, 0.50–1.97); length of hospital stay (P = 0.78); readmission (0.96, 0.80–1.22); and infection complications (local: 1.62 0.76–3.47; distant: 2.00, 0.18–22.08), were without significant difference, and so were adverse events or resistance emergence. No significant difference in clinical outcomes between 7 and 14 days of antibiotics was demonstrated in the subgroups of gender, age, hemodynamic status, immune status, and source of infection. Interpretation For patients hemodynamically stable and afebrile at 48 h prior to discontinuation, seven days of antibiotic therapy for enterobacterales bacteremia result in similar outcomes as 14 days, in terms of mortality, relapse, length of hospital stay, complications of infection, resistance emergence, and adverse events. These results apply for any adult age group, gender, source of infection, immune status, and hemodynamic status on presentation.

Contains fulltext : 287529.pdf (Publisher’s version ) (Open Access) Different views exist regarding the nature of patients' dependency in psychotherapy (trait versus contextual dependency), and its impact on treatment outcome and duration. Therefore we examined whether patients' levels of care dependency changed over time during a 9-month treatment period, and whether care dependency was related to symptom reduction and patients' wish for treatment continuation at the end of the treatment. Participants in this longitudinal study were 113 patients (Mage = 33.6, 78% female) with personality disorders receiving inpatient or daycare group psychotherapy. Both increases and decreases on different aspects of care dependency were found over the course of treatment. Decreases in dependency were related to larger symptom reduction, and higher levels of care dependency, especially patients' lack of perceived alternative options for the current treatment, were related to patients' stronger wish to continue their treatment. Changes in care dependency during treatment mainly supports the contextual view on patients' care dependency, and decreasing levels of dependency may have beneficial treatment effects. However, dependency may also lead to prolonged treatment duration. Clinical implications for therapists are presented. 11 p.

Background There is no standard treatment recommended at category 1 level in international guidelines for subsequent therapy after cyclin-dependent kinase 4/6 inhibitor (CDK4/6) based therapy. We aimed to evaluate which subsequent treatment oncologists prefer in patients with disease progression under CDKi. In addition, we aimed to show the effectiveness of systemic treatments after CDKi and whether there is a survival difference between hormonal treatments (monotherapy vs. mTOR-based). Methods A total of 609 patients from 53 centers were included in the study. Progression-free-survivals (PFS) of subsequent treatments (chemotherapy (CT, n:434) or endocrine therapy (ET, n:175)) after CDKi were calculated. Patients were evaluated in three groups as those who received CDKi in first-line (group A, n:202), second-line (group B, n: 153) and ≥ 3rd-line (group C, n: 254). PFS was compared according to the use of ET and CT. In addition, ET was compared as monotherapy versus everolimus-based combination therapy. Results The median duration of CDKi in the ET arms of Group A, B, and C was 17.0, 11.0, and 8.5 months in respectively; it was 9.0, 7.0, and 5.0 months in the CT arm. Median PFS after CDKi was 9.5 (5.0–14.0) months in the ET arm of group A, and 5.3 (3.9–6.8) months in the CT arm (p = 0.073). It was 6.7 (5.8–7.7) months in the ET arm of group B, and 5.7 (4.6–6.7) months in the CT arm (p = 0.311). It was 5.3 (2.5–8.0) months in the ET arm of group C and 4.0 (3.5–4.6) months in the CT arm (p = 0.434). Patients who received ET after CDKi were compared as those who received everolimus-based combination therapy versus those who received monotherapy ET: the median PFS in group A, B, and C was 11.0 vs. 5.9 (p = 0.047), 6.7 vs. 5.0 (p = 0.164), 6.7 vs. 3.9 (p = 0.763) months. Conclusion Physicians preferred CT rather than ET in patients with early progression under CDKi. It has been shown that subsequent ET after CDKi can be as effective as CT. It was also observed that better PFS could be achieved with the subsequent everolimus-based treatments after first-line CDKi compared to monotherapy ET.

The antibiotic treatment of periprosthetic joint infections (PJI) is complicated by the presence of biofilm produced by bacteria on the abiotic surface of the implant. Bacteria within the deeper layers of the biofilm become metabolically less active, resulting in antibiotic tolerance due to several mechanisms. This review describes the basic principles of antibiotic treatment in PJI in relation to the behavior of bacteria within the biofilm. The concept of biofilm-active antibiotics will be explained from an in vitro as well as in vivo perspective. Evidence from clinical studies on biofilm-active antibiotics in PJI will be highlighted, mainly focusing on the role of rifampicin for Gram-positive microorganisms and fluoroquinolones for Gram-negative microorganisms. The optimal treatment duration will be discussed as the timing of switching to oral antibiotic therapy.

BACKGROUND Little information exists regarding the incidence of chronic spontaneous urticaria (CSU) or differences in its characteristics according to age. OBJECTIVE To evaluate the incidence, clinical characteristics and treatment response of CSU according to age. METHODS The relevance of gender, age, history of allergic disease, pre-diagnosis duration, and treatment response were retrospectively evaluated in patients diagnosed with CSU at Pusan National University Hospital between 2011 and 2018. RESULTS A total of 970 patients were included in the study, consisting of 198 children and 772 adults. The CSU incidence increased during the study period in children, but not in adults. CSU was more common in adults than in children and the peak age of occurrence was 20-59 years. Increased female incidence was noted in adults, whereas patient and family allergic history was frequently observed in children than in adults. The overall rate of improvement was remarkably higher in children than in adults (P < 0.01), with pre-diagnosis duration and treatment duration both shorter in children than in adults. (P = 0.001). The proportion of men was higher and treatment duration was shorter in adolescence than in the other age groups, whereas the treatment duration was shorter in patients greater or equal to 60 years than in adults under 60 years, and the step 1 treatment rate was higher. CONCLUSION CSU incidence increased annually in children, but not in adults. The clinical characteristics and treatment response of CSU may differ depending on age and clinicians should be made aware of this fact.

Congenital ear anomalies are associated with psychological morbidity. Ear deformities can usually be corrected by nonsurgical techniques such as splinting or molding in the neonatal period, initiated before 6 weeks. Without early corrections, many will require otoplasty during childhood. We introduce a novel silicone-based custom mold technique for congenital ear anomalies. The highly malleable silicone was pushed into every part of the auricle, enabling the auricle to remain in the desired shape, with new molds made weekly. Of 31 newborns (18 males, 13 females), 54 ears were treated. Average age at treatment initiation was 26.8 days. The mean treatment duration was 43.2 days, with a median of 28 days. Normal appearance and parent's satisfaction were achieved in 30 patients with 49 deformed ears and also in four newborns older than 6 weeks. Three concha type microtia in two patients achieved great improvements and parents' satisfaction. No complications were reported. Marked aesthetic improvements and normal appearance were achieved for all deformed auricles treated, and improvements in the concha type microtia will partially alleviate future surgical corrections. The results are not inferior to other techniques. The advantages are as follows: cost-effective, time-saving, simple to master, no need for hair shaving, and easy use for parents. Patients older than 6 weeks of age achieved normal auricle appearance, enabling the correction in older newborns. Custom made silicone auricle molding offers a simple nonsurgical technique for correcting congenital ear anomalies, alleviating the need for future surgical corrections.

Pegylated interferon-alpha therapy is one of the first-line chronic hepatitis B treatment. Finite treatment duration, absence of drug resistance, delayed response, and higher hepatitis B surface antigen loss than nucleos(t)ides analog therapy are the advantages of pegylated interferon-alpha treatment. Common side effects and subcutaneous injections requirement limit its use. Identifying patients likely to respond to pegylated interferon-alpha and optimizing treatment is reasonable. Motivating patients to complete the 48-week treatment is necessary. Treatment is stopped or switched to other treatment strategies in patients with stopping rule criteria. Combination therapy with nucleos(t)ides analog may improve response, but remains controversial.

BACKGROUND Microneedling is a relatively novel therapeutic modality introduced in the 1990s where small, fine needles are used to create micro punctures in the skin. It is a minimally invasive procedure used for various dermatological conditions, including androgenetic alopecia (AGA). OBJECTIVE AND METHODS We comprehensively summarize the literature regarding microneedling in dermatology. We performed linear multivariable regressions to synthesize evidence from the clinical trials that investigated the efficacy of microneedling for AGA. Studies eligible for quantitative analyses were assessed for evidence quality. RESULTS The exact mechanism of microneedling action is yet to be determined, with theories that include the wound-healing cascade. Microneedling monotherapy significantly increased total hair count more than topical minoxidil 5% (β = 12.29; p

Anomalies present in about 30% of newborn ears; 15% to 20% of them are permanent. Malformations can be treated solely surgically; however, deformations, when promptly diagnosed, can be treated with nonsurgical methods, such as splinting and molding. The deformity of an outward curved concha is not only an aesthetic issue, but may confer functional problems that impair hearing and hearing aid usage. The goal of this report was to present this unique anomaly and our novel noninvasive treatment protocol for its management. Our cohort comprised 10 newborns treated for outward curved concha during 2018 and 2019. The patients underwent nonsurgical treatment using the EarWell system. In some patients, the management was followed by molding and taping to achieve the best effect. Treatment for all the patients began before age 3 weeks (mean, 2 weeks). Treatment duration was 5.2 weeks, on average. Nine patients did not show any adverse effects. The majority of parents expressed satisfaction with the aesthetic result; 70% were extremely pleased. Early initiation of the treatment-protocol for outward curved concha deformation yielded excellent and timely results in the infants, without the necessity of an invasive procedure.

Background We report the results of INICC surveillance study from 2013 to 2018, in 664 intensive care units (ICUs) in 133 cities, of 45 countries, from Latin-America, Europe, Africa, Eastern-Mediterranean, Southeast-Asia, and Western-Pacific. Methods Prospective data from patients hospitalized in ICUs were collected through INICC Surveillance Online System. CDC-NHSN definitions for device-associated healthcare-associated infection (DA-HAI) were applied. Results We collected data from 428,847 patients, for an aggregate of 2,815,402 bed-days, 1,468,216 central line (CL)-days, 1,053,330 mechanical ventilator (MV)-days, 1,740,776 urinary catheter (UC)-days. We found 7,785 CL-associated bloodstream infections (CLAB), 12,085 ventilator-associated events (VAE), and 5,509 UC-associated urinary tract infections (CAUTI). Pooled DA-HAI rates were 5.91% and 9.01 DA-HAIs/1,000 bed-days. Pooled CLAB rate was 5.30/1,000 CL-days; VAE rate was 11.47/1,000 MV-days, and CAUTI rate was 3.16/1,000 UC-days. P aeruginosa was non-susceptible (NS) to imipenem in 52.72% of cases; to colistin in 10.38%; to ceftazidime in 50%; to ciprofloxacin in 40.28%; and to amikacin in 34.05%. Klebsiella spp was NS to imipenem in 49.16%; to ceftazidime in 78.01%; to ciprofloxacin in 66.26%; and to amikacin in 42.45%. coagulase-negative Staphylococci and S aureus were NS to oxacillin in 91.44% and 56.03%, respectively. Enterococcus spp was NS to vancomycin in 42.31% of the cases. Conclusions DA-HAI rates and bacterial resistance are high and continuous efforts are needed to reduce them.

Summary Objectives Limited data exist on the optimal treatment duration for chronic pulmonary aspergillosis (CPA). We investigated the treatment outcome and recurrence rate according to treatment duration in CPA patients. Methods A total of 196 patients who completed at least 6 months of antifungal therapy (99% oral itraconazole) and achieved favorable treatment responses were analyzed. A Cox's proportional hazards regression model was used to adjust for potential confounding factors in the association between the duration of antifungal therapy (6–12 months vs. ≥ 12 months) and recurrence. Results All patients were treated with antifungal agents for at least 6 months (median: 12.5, interquartile range: 8.5–18.4 months) and categorized into 6–12 months group (79/196, 40%) and ≥ 12 months group (117/196, 60%). The 6–12 months group had significantly higher recurrence rates owing to CPA aggravation after the completion of treatment compared with the ≥ 12 months group (51% vs. 25%, P = 0.003). In a Cox's proportional hazards regression model, treatment duration ≥ 12 months was independently associated with a lower risk of recurrence (adjusted hazard ratio: 0.48, 95% confidence interval: 0.28–0.80). Conclusions Our data suggest that prolonging antifungal therapy beyond 12 months could reduce the recurrence rate in CPA patients.

Mild to moderate cases of periodontitis are usually efficiently treated in a nonsurgical way (i.e. subgingival curettage).The conventional approach uses hand instruments, which, however, is time-consuming and some patients may find itextremely uncomfortable, even in spite of anesthesia. Machine-driven curettage (especially sand-blasting) is not yet partof the everyday routine. Our aim was to share our initial experience with a new, combined, machine-driven approach tosubgingival curettage that we have lately introduced in our practice, in comparison with the conventional method. Thenew approach combines ultrasonic debridement and sand-blasting. We retrospectively analyzed the patients’ files whohad undergone curettage with either method in the period June, 2019 to February, 2020. Only non-smoking patients withmild to moderate periodontitis treated by the same periodontist and free of any systemic disease were eligible. Clinicalattachment level, mean pocket depth, plaque index, gingival bleeding index, treatment duration and patient satisfactionwere analyzed. Regarding their efficiency in reducing the indicators of inflammation, the two methods proved to be comparable:both caused significant reduction in almost all indicators. However, treatment duration was significantly shorterwith the machine-driven approach, and patients reported markedly less discomfort in connection with this approach.Within the limitations of our study, we conclude that machine-driven subgingival curettage (combined or not) may bea good alternative to the conventional manual approach in mild to moderate periodontitis, especially because it is moretime-efficient, less invasive and more comfortable to the patients.

During the course of fixed orthodontic therapy, patients should be instructed to eat specific food stuffs and beverages in order to maintain good health for the dentition and supporting structures and prevent frequent attachment debonding that prolong the treatment duration. After searching and collecting articles from 1930 till July 2021, the current review was prepared to emphasize various types of foods that should be taken during the course of fixed orthodontic therapy and to explain the effect of various food stuffs and beverages on the growth and development of craniofacial structures, tooth surfaces, root resorption, tooth movement, retention and stability after orthodontic treatment and the effect on the components of fixed orthodontic appliance.

Summary Background Treatment outcomes for Class III orthopaedic treatment are highly unpredictable and dependent on the timing of interception, age, and biological sex. Objective This systematic review aimed to assess the effects of sex dimorphism on outcomes and duration of orthopaedic treatment for Class III malocclusion in young children. Search methods Unrestricted search in six electronic databases until May 2021 was conducted. Supplemented by search in resources for published, unpublished literature, and ongoing trials. Selection criteria Randomized and non-randomized controlled trials reporting the use of Class III growth modification appliances, with baseline and outcome data for both sexes, were included. Data collection and analysis Study selection and data extraction were performed blindly and in duplicate by two reviewers. ROBINS-I, Cochrane Risk of Bias, and GRADE tools were used for certainty assessment. Results A total of 2429 records were screened. Four trials fulfilled the inclusion criteria, one was a randomized clinical trial (RCT) comparing facemask and facemask with mini-screw. Two clinical trials evaluated the effects of facemask appliance, one had a control group, another was prospective non-controlled. One compared the effects of the maxillary protraction bow appliance to a no treatment control. Two of the clinical trials were appraised as low and one was appraised as high risk of bias. The overall certainty of the available evidence was assessed as moderate. There was significant clinical heterogeneity in terms of methodology, type of intervention, and the measured outcomes, precluding a meta-analysis. Conclusions Minimal variations in sagittal, vertical, and dentoalveolar post-treatment cephalometric changes were reported between sexes. The available evidence is unclear to support these variations. Long-term-powered RCTs assessing cephalometric outcomes between sexes until the end of growth spurt and without pooling are not available, therefore, much needed. Registration PROSPERO database number CRD42020185797.

Background: The main aim of the study is to establish the prevalence of ocular surface disorders in glaucoma patients treated with topical antiglaucoma medications. Methods: Investigation of 50 eyes of 25 patients has been performed using two or more antiglaucoma medications for six months, and compared with 50 eyes of 25 normal subjects without any ocular problem. After one year each patient was evaluated by Schirmer’s (SCH) test-I Tear break-up time (TBUT), Corneal staining score. Results: The mean values in the glaucoma cases and control groups respectively were as follows: Schirmer’s test-1 (7.63 ± 2.64mm / 12.86 ± 1.93mm; p= 0.001), Tear breakup time (9.44 2 ±.76 sec / 11.8 ± 1.88 sec; p=0.001), Corneal staining score (5.7 ± 2.33 /1.1 ± 0.58; p=0.001). Conclusion: Patients on antiglaucoma therapy have a greater prevalence of ocular surface disease and dry eye. The causative factors were medications with preservatives and longer treatment duration. Keywords: Antiglaucoma medication, dry eye, ocular surface diseases (OSD), Schirmer’s (SCH) test, Tear breakup time, Corneal staining score.

Around half of all malocclusions that need orthodontic treatment are Class II in nature. Patients with Class II malocclusion primarily seek treatment for aesthetic improvement. Most of the skeletal class II malocclusions are because of mandibular deficiency, and can be best treated during the growing phase of development by removable functional appliances. The objective of this review is to evaluate and compare skeletal and dentoalveolar effects of various removable functional appliances in the treatment of class II malocclusion. Manual and electronic databases were searched, and out of 5,711 articles, 221 abstracts were shortlisted and reviewed. A total of 19 articles that fulfilled the selection criteria was then retrieved and analyzed. A significant increase in mandibular length and dentoalveolar effects with an increase in vertical dimension in a short time was observed with Twin-Block appliance treatment, followed by Bionator appliance treatment. The long-term stability of results achieved with Twin-Block appliance treatment is still questionable. In addition, Frankel appliance treatment effects are more skeletal in nature, with better control in the vertical dimension. However, it takes a more extended treatment duration to produce similar effects. Based on available evidence, we are convinced that removable functional appliances are valuable tools for correction of the Class II malocclusion at a growing age with a horizontal growth pattern.

Background The real-world treatment and outcomes of patients with anaplastic lymphoma kinase positive (ALK+) advanced non-small cell lung cancer treated with ALK Tyrosine Kinase Inhibitor (TKI) drugs in Sweden is not well described. Material and methods A retrospective population-based cohort study was conducted using Swedish national registers. All patients with a filled prescription for an ALK TKI between January 2012 and October 2020 were included. The sequencing of ALK TKI and duration of treatment (DOT) were described, and overall survival (OS) was estimated using the Kaplan-Meier method. Patients were stratified based on treatment with frontline chemotherapy, presence of CNS metastases prior to the first ALK TKI, and generation of ALK TKI agent. Results Among the total of 579 patients, 549 (95%) underwent a therapy sequence in line with current clinical practice with 204 (37%) patients receiving frontline chemotherapy. Single-line ALK TKI was given to 366 patients (crizotinib: 211; alectinib: 146; ceritinib: 9), whereas 128 patients received two different ALK TKI (frontline crizotinib: 100, alectinib: 24, ceritinib: 4); 40 patients received three lines and 15 patients four ALK TKI lines or more. With frontline chemotherapy, the mean (standard deviation) DOT was 1.07 (1.25) years for the entire TKI therapy sequence compared to 1.23 (1.28) years with frontline ALK TKI. The median (95% confidence interval) OS was 1.83 (1.48-2.13) years for the entire cohort, 1.44 (0.89-1.98) years for patients given frontline chemotherapy, and 2.02 (1.60-2.58) years for patients given frontline ALK TKI. Conclusion This study provides a unique overview of the patient population treated with ALK TKI in Sweden and reveals the treatment patterns applied in real clinical practice. More research is needed when longer follow-up data are available for later-generation ALK TKI, to fully understand ALK TKI sequencing and its effect on patient survival in a real-world setting. Funding Agencies|Pfizer

Diazoxide is the first-line treatment in children with hyperinsulinaemic hypoglycaemia (HH); however, limited information is available on the duration of diazoxide treatment in children who require over 2 years of it. Hence, we retrospectively reviewed the clinical and biochemical aspects, as well as the duration of therapy and neurodevelopmental assessment, in genetically uncharacterised diazoxide-responsive HH patients admitted to a tertiary hospital over the last 16 years, who had successfully discontinued diazoxide and remained euglycaemic. To exclude transient HH forms, only patients that required diazoxide for over 2 years were studied. We identified a total of 17 patients (70% males), in whom HH was diagnosed between 1 day and 18 months of age, and 88% were born at term with a median birth weight of 3.79 kg. All children responded to diazoxide at a median dose of 11.5 mg/kg/day, and it was stopped at a median age of 8.5 years, with a median duration of therapy of 7.25 years. The cases that required diazoxide the longest manifested no specific biochemical or clinical characteristics. Fasting tests performed after diazoxide discontinuation showed no longer requirement of diazoxide in all the cases. A total of 64.7% of the children showed mild to moderate developmental delay. Therefore, it seems that long-term resolution of HH in children with negative genetics for KATP channel genes who required diazoxide for over 2 years will ensue, and thus regular evaluation is crucial. The possible molecular mechanisms involved are unclear.

Menopausal hormone therapy (MHT) has been used for prevention and treatment of postmenopausal osteoporosis for several decades. However, public concerns were raised over the safety of MHT after the initial report was published in 2002 by the Women's Health Initiative. We conducted a historical review on this subject, primarily focusing on level I evidence from randomized controlled trials, systematic reviews and meta-analyses, and summarized high-quality evidence on the efficacy and safety of MHT in management of postmenopausal osteoporosis. Clinical issues were also discussed on MHT initiation, identification of treatment candidates and treatment duration, as well as discontinuation of MHT.

OBJECTIVE Historically, studies have shown that cranial remolding therapy improves surgical correction and protects against regression for patients with sagittal suture craniosynostosis. This study aimed to define the most responsive cranial height for measuring cephalic index (CI) following cranial remolding therapy for infants with sagittal suture craniosynostosis. METHODS The authors performed a retrospective analysis of data between January 2018 and August 2019. The outcomes measured were CI-3 (level of glabella) through CI-7 (superior to eurions), where each value was defined as the width at levels 3 through 7 divided by the length at level 3. Differences between baseline- and post-treatment measurements were assessed using a 5 × 2 repeated measures analysis of variance. RESULTS Data from thirty-four patients (19 males, 15 females, and mean age 2.79 months) were analyzed. Mean treatment duration was 4.59 ± 1.86 months. There was a significant increase between baseline and posttreatment measurements (baseline: 72.60% ± 0.70%, post: 76.30% ± 0.80%; F1,33 = 27.74, P

Introduction:The success of orthodontic therapy depends upon the knowledge and clinical skills of the orthodontist as well as awareness and sincerity of the patient. Due to long treatment duration, commitment and good rapport between both sides is essential. This retrospective study was undertaken to understand the factors affecting the reasons for discontinuation after commencement of treatment in a Government run hospital.Materials and method:A telephonic questionnaire survey was conducted on 153 patients who had discontinued treatment midway and their responses were analysed. The subjects were divided into 3 groups depending upon their school going years. The major focus areas were -1. Reasons for seeking orthodontic treatment 2. Reasons for pursuing treatment in this hospital and 3. Reasons for discontinuation of orthodontic treatment.Results and conclusions:Long waiting period before starting the treatment, failure to give subsequent appointments by the doctor, and having to leave the city were found to be the three most common causes for discontinuation. To reduce the attrition rate a three step strategy was devised to ensure an improved orthodontic outcome for the patients and to see more smiling faces bid adieu each year.

Orthodontic treatment that takes a long time carries a large risk of complications such as caries or root resorption. Various surgical and nonsurgical interventions have been performed, but non-surgical interventions are currently not widely accepted by orthodontists. Low Intensity Pulsed Ultrasound (LIPUS) is a form of non-invasive technology that has been used in the medical field for more than six decades. In the field of dentistry, LIPUS stimulation has been studied, among others, to improve bone remodelling, regeneration of cementum, gingiva and periodontal ligament. This article aims to review the mechanism of LIPUS in orthodontic tooth movement. This review is expected to become a clinical practice guide to shorten the duration of orthodontic treatment using LIPUS in the future.

Objective Comparison of studies on remission rates in pediatric Graves’ disease is complicated by lack of uniformity in treatment protocols, remission definition, and follow-up duration. We performed a systematic review on remission rates in pediatric Graves’ disease and attempted to create uniformity by recalculating remission rates based on an intention-to-treat analysis. Methods PubMed and Embase were searched in August 2020 for studies on patients with Graves’ disease: (i) 2 to 18 years of age, (ii) initially treated with methimazole or carbimazole for at least 18 months, (iii) with a follow-up duration of at least 1 year after cessation of methimazole or carbimazole. All reported remission rates were recalculated using an intention-to-treat analysis. Results Of 1890 articles, 29 articles consisting of 24 patient cohorts were included with a total of 3057 patients (82.6% female). Methimazole or carbimazole was initially prescribed in 2864 patients (93.7%). Recalculation based on intention-to-treat analysis resulted in an overall remission rate of 28.8% (829/2880). Pooled remission rates based on treatment duration were 23.7, 31.0, 43.7, and 75% respectively after 1.5–2.5 years, 2.5–5 years, 5–6 years (two studies), and 9 years (single study) treatment duration. The occurrence of adverse events was 419 in 2377 patients (17.6%), with major side effects in 25 patients (1.1%). Conclusions Using a standardized calculation, the overall remission rate in methimazole-treated pediatric GD is 28.8%. A few small studies indicate that longer treatment increases the remission rate. However, evidence is limited and further research is necessary to investigate the efficacy of longer treatment durations.

Objective: The present study was conducted to evaluate the effectiveness of treatment outcome using American Board of Orthodontics (ABO) scoring and total treatment time between labial and lingual appliance and also to assess patients’ perception of the lingual appliance system. Materials and Methods: Twenty patients requiring first premolar extraction were selected; 10 patients were treated with a lingual and 10 with a labial appliance. The treatment duration and ABO scores were recorded from the posttreatment dental casts and orthopantomogram (OPG). A questionnaire was used to evaluate the perception of patients on lingual treatment using a visual analogue scale (VAS). Results: The total ABO scores of the 2 groups were not statistically significant. The lingual- and labial-appliance treatments were completed in 19.30 ± 7.50 and 22.40 ± 6.35 months, respectively. The VAS showed that lingual-appliance patients experienced a moderate amount of pain and discomfort to the tongue and soft tissues. Patients did not have considerable difficulty with speech and in maintaining oral hygiene. Conclusion: Lingual appliance cases finished with a comparable quality of orthodontic treatment precision well within the normal treatment time frame. These patients had moderate difficulties with speech, tongue irritation, and pain. They did not have difficulty in maintaining their oral hygiene and were satisfied with their smile and treatment outcome.

Introduction Therapeutic options for metastatic castration-resistant prostate cancer (mCRPC) patients are continuously advancing. We described mCRPC treatment patterns in the US from 2013 to 2019. Methods Patients with a confirmed mCRPC diagnosis and adenocarcinoma histology were included in the US Flatiron Health Electronic Health Record-derived de-identified database. Treatment patterns [including treatment per lines of therapies (LOTs), LOT sequences, and time on treatment] and overall survival (OS) have been described in mCRPC settings. Results Of 5213 patients (mean age: 72.6 years), 4374 (83.9%) were treated with ≥ 1 LOT post-mCRPC diagnosis (among those with ≥ 1 LOT, 55.3%, 29.5%, 14.7%, and 6.7% had ≥ 2, 3, 4, and 5 LOTs, respectively). In first line (1L), the main treatment class was next-generation hormonal agents (NHA; 62.5% of patients with ≥ 1 LOT), while the shortest and longest time on 1L were observed for chemotherapy (median 2.8 months) and NHA (median 5.1 months), respectively. The most common LOT sequences were NHA → NHA (29.4% of patients with ≥ 2 LOTs) and NHA → NHA → chemotherapy (16.7% of patients with ≥ 3 LOTs). In Kaplan–Meier analyses, the median OS was 19.4, 14.6, and 11.1 months post-1L, 2L, and 3L start, respectively. Patients who moved rapidly through LOTs had an increased risk of death. Conclusions NHA were widely used as 1L therapy in mCRPC patients from 2013 to 2019, but time on 1L NHA treatment was on average

Ibrutinib has superior progression-free survival compared with bendamustine plus rituximab (BR) in older CLL patients, however, differences in treatment duration, six monthly BR cycles versus continuous ibrutinib, complicate adverse event (AE) comparisons. We introduce the AE burden score (AEsc) to compare AEs, calculated for each patient by summing over products of reporting period length and grade for each all-cause grade 1-4 AE and dividing by the length of time over which AEs are assessed. A total of 176 patients received BR and 361 ibrutinib alone or with six cycles of rituximab. At 38 months median follow-up, 64% remained on ibrutinib. Median AEsc was higher with BR versus ibrutinib in the first six cycles (7.2 versus 4.9, p < 0.0001). Within ibrutinib arms, median AEsc decreased significantly to 3.7 after six cycles (p < 0.0001). 10% and 14% of BR and ibrutinib patients discontinued treatment for AEs. In ibrutinib arms, cumulative incidence of grade 3 or higher atrial fibrillation, hypertension, and infection (AEs of clinical interest) at 12 months was 4.5%, 17.5%, and 12.8%, respectively, and increased more slowly thereafter to 7.7%, 25.4%, and 20.5% at 36 months. Analytical tools including the AEsc and cumulative incidence of AEs can help to better characterize AE burden over time. ClinicalTrials.gov identifier: NCT01886872.

Photobiomodulation (PBM) uses low-intensity visible or near-infrared light to produce beneficial effects on cells or tissues, such as brain therapy, wound healing. Still there is no consistent recommendation on the parameters (dose, light mode, wavelength, irradiance) and protocols (repetition, treatment duration) for its clinical application. Herein, we summarize the current PBM parameters for the treatment of melanoma, and we also discuss the potential photoreceptors and downstream signaling mechanisms in the PBM treatment of melanoma cells. It is hypothesized that PBM may inhibit the melanoma cells by activating mitochondria, OPNs, and other receptors. Regardless of the underlying mechanisms, PBM has been shown to be beneficial in treating melanoma. Through further in-depth studies of the underlying potential mechanisms, it can strengthen the applications of PBM for the therapy of melanoma.

Pharmacomechanical thrombolysis (PMT) and catheter-directed thrombolysis (CDT) are frequently employed for treating deep venous thrombosis (DVT). However, there have been relatively few studies comparing PMT outcomes to those associated with CDT. The present study was thus designed to compare short- and mid-term PMT and CDT patient outcomes following the treatment of DVT of the lower extremities.This study was a retrospective analysis of 98 patients treated at the 3rd Affiliated Hospital of Shenzhen University (Shenzhen, China) and Beijing Chao Yang Hospital (Beijing, China). All patients had undergone treatment for symptomatic DVT of the lower legs via either CDT or PMT. Clinical records and outcome data between the patients in these 2 treatment groups were compared.Of the 98 patients analyzed in this retrospective study, 50 had been treated via CDT while 48 had undergone PMT. These PMT and CDT operations were associated with mean treatment durations of 0.97 ± 0.20 hr and 32.48 ± 7.46 hr, respectively (P0.0001). Complete lysis was achieved in 78 patients (42 and 36 in the PMT and CDT groups, respectively P = 0.057), while effective lysis was achieved in 96 patients (48 and 48 in the PMT and CDT groups, respectively P = 0.162), with lysis being ineffective in the 2 remaining patients. PMT was associated with a significantly decreased length of hospital stay, usage of UK dose, and treatment duration relative to CDT(P0.0001). No major complications or MACE incidence were noted in either group, although 18 patients in the PMT group suffered from bradyarrhythmia (P = 0.007). Clinical efficacy was achieved in 96 patients (48 in each treatment group) at time of discharge (P = 0.162). A Kaplan-Meier analysis revealed that 2-year primary patency rates did not differ significantly between these 2 groups (P = 0.442).PMT is an effective treatment modality in patients with symptomatic DVT. Relative to CDT it is associated with high treatment success rates, reduced treatment duration, and reduced hospitalization duration, although it is also associated with higher rates of systemic complications.

Prolonged treatment duration is one of the main concerns of patients undergoing orthodontic treatment. In addition to the longer duration, there are several drawbacks such as increased predisposition to root resorption, caries, and gingival recession. Thus, clinicians are always on the lookout for better solutions or alternatives. This is where the technique of corticotomy came in. In the present study, two cases where a piezosurgical corticotomy was done for rapid tooth movement have been discussed. The entire treatment duration was about 7–8 months without any relapse or posttreatment complications.

Summary In a 1945 Nobel Lecture, Sir Alexander Fleming warned against the overuse of antibiotics, particularly in response to public pressure. In the subsequent decades, evidence has shown that bacteria can become resistant to almost any available molecule. One key question is how the emergence and dissemination of resistant bacteria or resistance genes can be delayed. Although some clinicians remain sceptical, in this Personal View, we argue that the prescription of fewer antibiotics and shorter treatment duration is just as effective as longer regimens that remain the current guideline. Additionally, we discuss the fact that shorter antibiotic treatments exert less selective pressure on microorganisms, preventing the development of resistance. By contrast, longer treatments associated with a strong selective pressure favour the emergence of resistant clones within commensal organisms. We also emphasise that more studies are needed to identify the optimal duration of antibiotic therapy for common infections, which is important for making changes to the current guidelines, and to identify clinical biomarkers to guide antibiotic treatment in both hospital and ambulatory settings.

5-Azacitidine (5-AZA) is widely used for the treatment of higher-risk myelodysplastic syndromes. However, response and survival rates vary considerably, while indicated treatment duration remains undefined. For these reasons, factors determining response and survival are of major importance. Clinical, morphological, flow cytometry, cytogenetic and molecular factors are discussed in this review. Biomarkers predictive of response and prognosis, as well as their link to the mode of action of 5-AZA are also addressed, shifting the focus from clinical practice to investigational research. Their use could further improve prognostic classification of 5-AZA treated higher-risk myelodysplastic syndromes in the near future.Lay abstract Myelodysplastic syndrome is a disorder in which patients have dysfunctional blood cells. The only chance of curing patients with high-risk myelodysplastic syndrome (HR-MDS) is allogeneic stem cell transplantation. However, most HR-MDS patients are not young or fit enough to receive such a toxic treatment. For these patients, hypomethylating drugs such as 5-azacitidine (5-AZA) and decitabine are preferable treatments. These drugs work by reducing the number of molecules known as methyl groups that are attached to DNA, which can lead to cell death. About half of patients respond to it, and those who do respond, survive longer than those who do not. In addition, 5-AZA delays disease progression from HR-MDS to acute myeloid leukemia, a type of blood cancer, and may help patients who do not improve to live longer. However, 5-AZA has side effects that can be hard to bear, such as an increased need for red blood cells and/or platelet transfusions. For this reason, it would be good to predict the clinical and biological factors associated with either response or final outcome following treatment. In this manuscript, we attempt to summarize current knowledge on this topic.

Color changes were tested and compared for heat-treated Paulownia tomentosa and Pinus koraiensis wood treated with hot oil or hot air for further utilization of these species. Hot oil and hot air treatments were conducted at 180, 200, and 220 °C for 1, 2, and 3 h. Heat-treated wood color changes were determined using the CIE-Lab color system. Weight changes of the wood before and after heat treatment were also determined. The weight of the oil heat-treated wood increased considerably but it decreased in air heat-treated wood. The oil heat-treated samples showed a greater decrease in lightness (L*) than air heat-treated samples. A significant change in L* was observed in Paulownia tomentosa. The red/green chromaticity (a*) of both wood samples increased at 180 and 200 °C and slightly decreased at 220 °C. The yellow/blue chromaticity (b*) in both wood samples increased at 180 °C, but it rapidly decreased with increasing treatment durations at 200 and 220 °C. The overall color change (ΔE*) in both heat treatments increased with increasing temperature, being higher in Paulownia tomentosa than in Pinus koraiensis. In conclusion, oil heat treatment reduced treatment duration and was a more effective method than air heat treatment in improving wood color.

Background Mass drug administration (MDA) with ivermectin is the main strategy for onchocerciasis elimination. Ivermectin is generally safe, but is associated with serious adverse events in individuals with high Loa loa microfilarial densities (MFD). Therefore, ivermectin MDA is not recommended in areas where onchocerciasis is hypo-endemic and L loa is co-endemic. To eliminate onchocerciasis in those areas, a test-and-not-treat (TaNT) strategy has been proposed. We investigated whether onchocerciasis elimination can be achieved using TaNT and the required duration. Methods We used the individual-based model ONCHOSIM to predict the impact of TaNT on onchocerciasis microfilarial (mf) prevalence. We simulated precontrol mf prevalence levels from 2% to 40%. The impact of TaNT was simulated under varying levels of participation, systematic nonparticipation, and exclusion from ivermectin resulting from high L loa MFD. For each scenario, we assessed the time to elimination, defined as bringing onchocerciasis mf prevalence below 1.4%. Results In areas with 30% to 40% precontrol mf prevalence, the model predicted that it would take between 14 and 16 years to bring the mf prevalence below 1.4% using conventional MDA, assuming 65% participation. TaNT would increase the time to elimination by up to 1.5 years, depending on the level of systematic nonparticipation and the exclusion rate. At lower exclusion rates (≤2.5%), the delay would be less than 6 months. Conclusions Our model predicts that onchocerciasis can be eliminated using TaNT in L loa co-endemic areas. The required treatment duration using TaNT would be only slightly longer than in areas with conventional MDA, provided that participation is good., Our model predicts that onchocerciasis can be eliminated using test-and-not-treat (TaNT) in L loa co-endemic areas. The required treatment duration using TaNT would be only slightly longer than in areas with conventional mass drug administration, provided that participation is good.

A pulsed electromagnetic field (PEMF) can promote osteogenesis. However, studies have shown variation in the signal characteristics in terms of waveform type, intensity, frequency, and treatment duration. Among the factors that affect electromagnetic fields, frequency plays a major role. However, few studies have investigated the effects of PEMF at different frequencies in osteoporotic mice. Therefore, our objective was to determine the effect of PEMF frequency in osteoporotic mice. Forty 3-month-old female mice were randomly divided into the following five groups: sham, OVX, and OVX followed by 1.6-mT PEMF exposure groups (8 Hz, 50 Hz, and 75 Hz, 1.6 mT). The PEMF was applied for 1 h/day, 7 days/week, for 4 weeks. After 4 weeks, the micro-computed tomography showed that PEMF with (50 and 75 Hz) ameliorated the deterioration of bone microarchitecture. Improvements in the bone histological analysis were identified for PEMF with 50 and 75 Hz groups compared with the ovariectomy (OVX) controls. Osteoclast numbers were decreased in PEMF with (50 and 75 Hz). Moreover, the real-time PCR demonstrated PEMF with (50 and 75 Hz) significantly promoted the expression of the osteoblast-related genes (ALP, OCN, Runx2), and increased the serum PINP. PEMF with (50 and 75 Hz) exerted significant inhibitory effects on the osteoclast-related mRNA expression (CTSK, NFATc1, TRAP) and bone resorption markers CTX-I and IL-1β. Taken together, our results showed that PEMF at 50 and 75 Hz with 1.6 mT significantly ameliorate the deterioration of bone microarchitecture in OVX mice. The inhibitory effect of PEMF may be associated with IL-1β inhibition. © 2021 Bioelectromagnetics Society.

We report a general strategy to develop injectable welded nanofibers to facilitate the outgrowth and extension of neurites. In this case, nonwoven mats of uniaxially aligned poly(caprolactone)(PCL) nanofibers were firstly cut into several small pieces with fixed fiber lengths of 25, 50 and 100 µm, respectively, using a cryotome. A tissuelyser was employed to homogenize and disperse the short nanofibers to a homogeneous suspension. By tuning treatment duration from 100 s to 400 s, the temperature of the suspension was brought close to the melting point of PCL. As such, the short nanofibers were welded at their cross points while the fibers far away from the cross points remain the original structures. We showed that the viability of neuroblastoma SH-SY5Y cells and their neurite outgrowth and extension were enhanced with the use of such welded short nanofibers. Taken together, this study provides a simple way to generate injectable welded nanofibers, holding potential in affecting neurite outgrowth and extension for nerve repair, in particular, in the central nervous system.

Xiaomeng Xu,1 Dominique Milea,1 Aldo Amador Navarro Rojas,1 Anthony Braganza,1 Tim Holbrook,2 Brett Marett,3 Robert Young,4 Raewyn J Scott,4 Barry Gribben5 1Value Evidence and Outcomes, GlaxoSmithKline plc., 139234, Singapore; 2Real World Evidence, Adelphi Real World, Bollington, Macclesfield, Cheshire, UK; 3Medical Affairs, GlaxoSmithKline NZ Limited, Auckland, 1010, New Zealand; 4Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand; 5CBG Health Research Limited, Faculty of Medical and Health Sciences, Auckland, New ZealandCorrespondence: Xiaomeng XuValue Evidence and Outcomes, GlaxoSmithKline Plc., 23 Rochester Park, 139234, SingaporeTel +65 81616659Email Xiaomeng.x.xu@gsk.comPurpose: Real-world data on maintenance treatment and prescription patterns provide insights into healthcare management among patients with chronic obstructive pulmonary disease (COPD), which benefits our understanding of current COPD treatment patterns in New Zealand.Methods: We retrospectively analyzed real-world data from the HealthStat general practice database to evaluate treatment patterns among patients with COPD in New Zealand who initiated multiple-inhaler triple therapy (MITT): inhaled corticosteroid (ICS) + long-acting muscarinic antagonist + long-acting β2-agonist (LABA). Our main objective described treatment patterns (class, duration, modification, persistence, and adherence) and characteristics of patients with COPD initiating MITT between 1 May 2016 and 30 April 2017, with 12-months’ follow-up. We also assessed the number of patients receiving MITT between 2015 and 2017, among a larger patient population receiving long-acting bronchodilator and ICS-containing therapies.Results: Of 6249 eligible patients, 421 (mean age 67.3 years; mean numberexacerbations at baseline 1.8) initiated MITT: 59.1% received combination ICS/LABA therapy prior to MITT initiation, and median treatment duration prior to MITT initiation was 350 days. Overall, 33.5% of patients remained on index treatment for 12 months. Of the remaining patients who modified treatment (on average at 144.4 days), those who had a direct switch (24.9%) or retreatment (13.5%) remained on MITT, 19.7% of patients stepped down to mono/dual therapy, and 8.3% discontinued treatment. Mean (standard deviation) persistence to any MITT over 12 months was 47.3 (50.0), and 53.4% of patients were considered adherent to MITT. Total proportions of patients receiving long-acting bronchodilator therapy and MITT increased between 2015 and 2017.Conclusion: Most patients with COPD in New Zealand who initiated MITT had characteristics appropriate for triple therapy prescription, suggesting prescription behavior among general practitioners was largely consistent with treatment guidelines. Our findings may help optimize treatment decisions, with a focus on improving long-term triple therapy persistence and adherence.Keywords: chronic obstructive pulmonary disease, inhaled corticosteroid, long-acting β-agonist, long-acting muscarinic antagonist, New Zealand, multiple-inhaler triple therapy

Background Given the persistently high global burden of tuberculosis, effective and shorter treatment options are needed. We explored the relationship between relapse and treatment length as well as interregimen differences for 2 novel antituberculosis drug regimens using a mouse model of tuberculosis infection and mathematical modeling. Methods Mycobacterium tuberculosis–infected mice were treated for up to 13 weeks with bedaquiline and pretomanid combined with moxifloxacin and pyrazinamide (BPaMZ) or linezolid (BPaL). Cure rates were evaluated 12 weeks after treatment completion. The standard regimen of isoniazid, rifampicin, pyrazinamide, and ethambutol (HRZE) was evaluated as a comparator. Results Six weeks of BPaMZ was sufficient to achieve cure in all mice. In contrast, 13 weeks of BPaL and 24 weeks of HRZE did not achieve 100% cure rates. Based on mathematical model predictions, 95% probability of cure was predicted to occur at 1.6, 4.3, and 7.9 months for BPaMZ, BPaL, and HRZE, respectively. Conclusion This study provides additional evidence for the treatment-shortening capacity of BPaMZ over BPaL and HRZE. To optimally use preclinical data for predicting clinical outcomes, and to overcome the limitations that hamper such extrapolation, we advocate bundling of available published preclinical data into mathematical models.

The effect of antioxidants depends on several factors, including the type, dose, timing, and treatment duration. Several studies have demonstrated that antioxidants can prevent age-related hearing ...

To assess the safety and serum estradiol (E2) and total testosterone (T) concentrations in postmenopausal women treated with Pellet Hormonal Therapy (PHT) and Food and Drug Administration approved Hormonal Therapy (FHT).A total of 539 postmenopausal women were identified, including 384 on PHT and 155 on FHT. Data extracted from medical records include demographics, indication for hormone therapy, treatment duration, side effects, serum E2 and T levels, and frequency of laboratory follow-up.The incidence of overall side effects was significantly higher in PHT compared with FHT (221 [57.6%] vs 23 [14.8%], P 0.00001, odds ratio [95% CI] =8.0[4.5-14.2]). When examining women with an intact uterus prior to hormone therapy initiation, 55.3% (136/246) on PHT vs 15.2% (12/79) on FHT had at least one episode of abnormal uterine bleeding (P 0.0001, odds ratio [95% CI] = 7.9[3.6-17.0]). Furthermore, a significantly higher proportion of women on PHT (20.3% [50/246]), compared with 6.3% (5/79) on FHT, had a hysterectomy (P = 0.036, odds ratio [95% CI] = 3.2[1.1-9.3]). Both mean (SD, Min-Max) peak E2 (pg/mL) and peak T (ng/dL) are significantly higher in the PHT group than those in the FHT group (E2: 237.70 [168.55, 10-1,111] vs 93.45 [130.77, 5.5-465.8], T: 194.04 [84.94, 4.3-599] vs 15.59 [19.52, 0.2-70], P 0.00001). Of those on PHT, four women had E2 level1,000 pg/mL and nine women with T level400 ng/dL.Women on PHT had a significantly higher incidence of side effects than FHT as well as a significantly higher supraphysiological level of peak E2 and T during the treatment.