Nascent MSKIK peptide cancels ribosomal stalling by arrest peptides in Escherichia coli.

The insertion of the DNA sequence encoding SKIK peptide adjacent to the M start codon of a difficult-to-express protein enhances protein production in Escherichia coli. In this report, we reveal that the increased production of the SKIK-tagged protein is not due to codon usage of the SKIK sequence. Furthermore, we found that insertion of SKIK or MSKIK just before the SecM arrest peptide (FSTPVWISQAQGIRAGP), which causes ribosomal stalling on mRNA, greatly increased the production of the protein containing the SecM arrest peptide in the E. coli-reconstituted cell-free protein synthesis system (PURE system). A similar translation enhancement phenomenon by MSKIK was observed for the CmlA leader peptide, a ribosome arrest peptide, whose arrest is induced by chloramphenicol. These results strongly suggest that the nascent MSKIK peptide prevents or releases ribosomal stalling immediately following its generation during the translation process, resulting in an increase of protein production.

Initial treatment choices for long-term remission of chronic insomnia disorder in adults: a systematic review and network meta-analysis.

BACKGROUND: We aimed to evaluate the comparative efficacy and acceptability of cognitive behavioral therapy for insomnia (CBT-I), pharmacotherapy, and their combination in the long and short terms among adults with chronic insomnia disorder. METHODS: We searched multiple databases to December 27, 2023. We included trials in hypnotic-free adults with chronic insomnia comparing at least two of CBT-I, pharmacotherapy, or their combination. We assessed the confidence in evidence using CINeMA. The primary outcome was long-term remission. Secondary outcomes included all-cause dropout and self-reported sleep continuity measures in the long term, and the same outcomes in the short term. We performed frequentist random-effects network meta-analyses (CRD42024505519). FINDINGS: We identified 13 trials including 823 randomized participants (mean age, 47.8 years; 60% women). CBT-I was more beneficial than pharmacotherapy in the long term (median duration, 24 weeks [range, 12 to 48 weeks]; remission odds ratio, 1.82 [95% confidence interval (CI), 1.15-2.87]; [certainty of evidence: high]), while there was weaker evidence of benefit of combination against pharmacotherapy (1.71 [95% CI, 0.88-3.30: moderate]) and no clear difference of CBT-I against combination (1.07 [95% CI, 0.63-1.80: moderate]). CBT-I was associated with fewer dropouts than pharmacotherapy. Short-term outcomes favored CBT-I over pharmacotherapy except total sleep time. Given the average long-term remission rate in the pharmacotherapy-initiating arms of 28%, CBT-I resulted in a long-term remission rate of 41% (95% CI, 31%-53%) and combination 40% (95% CI, 25%-56%). INTERPRETATION: The current study found that starting with CBT-I for chronic insomnia leads to better outcomes than pharmacotherapy. Combination may be better than pharmacotherapy alone, but unlikely to be worth the additional burden over CBT-I alone.

[BRONCHOPULMONARY ASPERGILLOSIS WITH COMORBID GRANULOMATOUS POLYANGIITIS IN A PATIENT WHO PRESENTED WITH EXOPHTHALMOS: A CASE REPORT].

There have been no reports of the coexistence of allergic bronchopulmonary aspergillosis (ABPA) and granulomatosis with polyangiitis (GPA). The first case of ABPA with comorbid GPA that developed exophthalmos is reported. A 69-year-old man was referred to our hospital for exophthalmos, fever, anorexia and weight loss. The patient had been diagnosed with ABPA six years earlier, which had been repeatedly treated but recurred with oral corticosteroids with or without antifungal therapy. The laboratory data on referral showed elevations of the white blood cell count, C-reactive protein and specific immunoglobulin E against Aspergillus fumigatus, but antineutrophil cytoplasmic antibody was not positive. Urinalysis showed proteinuria. Paranasal sinus and chest computed tomography showed sinusitis with osteochondral destruction, bronchiectasis, mucus plugging, and a pulmonary nodule. Orbital magnetic resonance imaging showed swelling of the medial rectus muscle and peripheral mass. The intraorbital tissue biopsy showed a necrotic granuloma and necrotizing vasculitis. The patient was diagnosed with GPA, on the basis of the Ministry of Health, Labour and Welfare's criteria of Japan. The patient was treated with induction therapy consisting of glucocorticoids and rituximab, and his symptoms improved. Though the pathogenesis common to ABPA and GPA remains unknown, neutrophilic inflammation induced by airway Aspergillus persistent infection might be involved. Study of further cases is needed.

Optimal dose of aripiprazole for augmentation therapy of antidepressant-refractory depression: preliminary findings based on a systematic review and dose-effect meta-analysis.

BACKGROUND: Aripiprazole augmentation is proven effective for antidepressant-refractory depression, but its licensed dose range is wide and optimal dosage remains unclear. AIMS: To find the optimal dosage of aripiprazole augmentation. METHOD: Multiple electronic databases were searched (from inception to 16 February 2021) to identify all assessor-masked randomised controlled trials evaluating aripiprazole augmentation therapy in adults (≥18 years old, both genders) with major depressive disorder showing inadequate response to at least one antidepressant treatment. A random-effects, one-stage dose-effect meta-analysis with restricted cubic splines was conducted. Outcomes were efficacy (treatment response: ≥50% reduction in depression severity), tolerability (drop-out due to adverse effects) and acceptability (drop-out for any reason) after 8 weeks of treatment (range 4-12 weeks). RESULTS: Ten studies met the inclusion criteria. All were individually randomised, placebo-controlled, multi-centre, parallel studies including 2625 participants in total. The maximum target dose-efficacy curve showed an increase up to doses between 2 mg (odds ratio OR = 1.46, 95% CI 1.15-1.85) and 5 mg (OR = 1.93, 95% CI 1.33-2.81), and then a non-increasing trend through the higher licensed doses up to 20 mg (OR = 1.90, 95% CI 1.52-2.37). Tolerability showed a similar trend with greater uncertainty. Acceptability showed no significant difference through the examined dose range. Certainty of evidence was low to moderate. CONCLUSIONS: Low-dose aripiprazole as augmentation treatment might achieve the optimal balance between efficacy, tolerability and acceptability in the acute treatment of antidepressant-refractory depression. However, the small number of included studies and the overall moderate to high risk of bias seriously compromise the reliability of the results. Further research is required to investigate the benefits of low versus high dose.

Optimal dose of brexpiprazole for augmentation therapy of antidepressant-refractory depression: A systematic review and dose-effect meta-analysis.

BACKGROUND: Brexpiprazole augmentation is an effective treatment strategy for antidepressant-refractory depression, but its optimal dosage remains unclear. AIMS: To find the optimal dosage of brexpiprazole as augmentation of other antidepressants. METHODS: We searched multiple electronic databases (from inception to September 16th, 2021) to identify double-blind, randomized placebo-controlled fixed-dose trials evaluating brexpiprazole augmentation therapy in adults (≥18 years old, both genders) with major depressive disorder not adequately responding to one or more antidepressant treatment. Our outcomes of interest at 8 weeks (range 4-12 weeks) were efficacy (treatment response defined as 50% or greater reduction in depression severity), tolerability (dropouts due to adverse effects) and acceptability (dropouts for any reason). We performed a random-effects, one-stage dose-effect meta-analysis with restricted cubic splines. RESULTS: Six studies met the inclusion criteria, including 1671 participants in total. The dose-efficacy curve showed an increase up to doses around 2 mg (odds ratio [OR] 1.52, 95% confidence interval [CI] 1.12-2.06) and then a decreasing trend through the higher licensed dose up to 3 mg (OR 1.40, 95% CI 0.95-2.08). The shape of the dose-tolerability curve was comparable to that of the efficacy and the dose-acceptability curve showed a monotonic increasing trend but both had wide confidence bands. CONCLUSIONS: One to two milligrams of brexpiprazole as augmentation treatment may achieve an optimal balance between efficacy, tolerability, and acceptability in the acute treatment of antidepressant-refractory depression. However, the small number of included studies limit the reliability of the results. Further research is required to validate the findings.

Effects of KnockOut Serum Replacement on Differentiation of Mouse-Induced Pluripotent Stem Cells into Odontoblasts.

Serum serves as a source of rich nutrients during in vitro cell culture, facilitating cell adhesion, growth, and differentiation. When culturing stem cells for transplantation, however, it must be remembered that such culture medium may contain substances potentially harmful to the proposed recipient and may even induce cellular damage. The purpose of this study was to determine whether KnockOut Serum Replacement (KSR), a chemically defined medium supplement, enhanced in vitro differentiation of induced pluripotent stem cells into odontoblasts. Cranial neural crest cells, precursors of odontoblasts, were generated from mouse-induced pluripotent stem cells. They were then cultured in serum-free Dulbecco's modified Eagle's/F12 medium containing fibroblast growth factor 8 with or without KSR. The cells cultured with KSR showed strong proliferation, acquired a spindle-like morphology, and connected with the surrounding cells. KnockOut Serum Replacement also boosted expression of odontoblast markers as measured by qRT-PCR, and increased dentin sialoprotein as assessed by immunostaining. These results confirmed that mouse-induced pluripotent stem cells differentiated into odontoblasts under serum-free conditions, and that KSR enhanced the efficiency of this process.

Fluxametamide: A novel isoxazoline insecticide that acts via distinctive antagonism of insect ligand-gated chloride channels.

Fluxametamide is a novel wide-spectrum insecticide that was discovered and synthesized by Nissan Chemical Industries, Ltd. To identify the mode of action of fluxametamide, we first performed [3H]4'-ethynyl-4-n-propylbicycloorthobenzoate (EBOB) binding assays. Fluxametamide potently inhibited the specific binding of [3H]EBOB to housefly-head membranes, suggesting that fluxametamide affects insect γ-aminobutyric acid (GABA)-gated chloride channels (GABACls). Next, the antagonism of housefly GABACls and glutamate-gated chloride channels (GluCls) was examined using the two-electrode voltage clamp (TEVC) method. Fluxametamide inhibited agonist responses in both ion channels expressed in Xenopus oocytes in the nanomolar range, indicating that this insecticide is a ligand-gated chloride channel (LGCC) antagonist. The insecticidal and LGCC antagonist potencies of fluxametamide against fipronil-susceptible and fipronil-resistant strains of small brown planthoppers and two-spotted spider mites, which are insensitive to fipronil, were evaluated. Fluxametamide exhibited similar levels of both activities in these fipronil-susceptible and fipronil-resistant arthropod pests. These data indicate that fluxametamide exerts distinctive antagonism of arthropod GABACls by binding to a site different from those for existing antagonists. In contrast to its profound actions on the arthropod LGCCs, the antagonistic activity of fluxametamide against rat GABACls and human glycine-gated chloride channels was nearly insignificant, suggesting that fluxametamide has high target-site selectivity for arthropods over mammals. Overall, fluxametamide is a new type of LGCC antagonist insecticide with excellent safety for mammals at the target-site level.

Comparative Efficacy and Acceptability of Treatment Strategies for Antipsychotic-Induced Akathisia: A Systematic Review and Network Meta-analysis.

BACKGROUND: Antipsychotics are the treatment of choice for schizophrenia, but they often induce akathisia. However, comparative efficacy of treatment strategies for akathisia remains unclear. DESIGN: We performed a systematic review and network meta-analyses (PROSPERO CRD42023450720). We searched multiple databases on July 24, 2023. We included randomized clinical trials comparing 1 or more treatment strategies for antipsychotic-induced akathisia against each other or control conditions. We included adults with schizophrenia or other psychiatric disorders treated with antipsychotics. The primary outcome was akathisia severity at posttreatment. Secondary outcomes included akathisia response, all-cause dropout, psychotic symptoms, and long-term akathisia severity. We synthesized data in random effects frequentist network meta-analyses and assessed confidence in the evidence using CINeMA. RESULTS: We identified 19 trials with 661 randomized participants (mean age 35.9 [standard deviation 12.0]; 36.7% [195 of 532] women). No trials examined dose reduction or switching of antipsychotics. Findings suggested 5-HT2A antagonists (k = 6, n = 108; standardized mean difference [SMD] -1.07 [95% confidence interval, -1.42; -0.71]) and beta-blockers (k = 8, n = 105; SMD -0.46 [-0.85; -0.07]) may improve akathisia severity, but confidence in the evidence was deemed low. We also found that benzodiazepines (k = 2, n = 13; SMD -1.62 [-2.64; -0.59]) and vitamin B6 (k = 3, n = 67; SMD -0.99 [-1.49; -0.50]) might also be beneficial, but confidence in the evidence was very low. Analyses of secondary outcomes did not provide additional insights. CONCLUSIONS: Our findings suggest that 5-HT2A antagonists, beta-blockers, and with a lesser certainty, benzodiazepines, and vitamin B6 might improve akathisia. Given the low to very low confidence in the evidence of add-on agents and the absence of evidence of their long-term efficacy, careful consideration of side effects is warranted. These recommendations are extremely preliminary and further trials are needed.

Understanding effect size: an international online survey among psychiatrists, psychologists, physicians from other medical specialities, dentists and other health professionals.

BACKGROUND AND OBJECTIVE: Various ways exist to display the effectiveness of medical treatment options. This study examined various psychiatric, medical and allied professionals' understanding and perceived usefulness of eight effect size indices for presenting both dichotomous and continuous outcome data. METHODS: We surveyed 1316 participants from 13 countries using an online questionnaire. We presented hypothetical treatment effects of interventions versus placebo concerning chronic pain using eight different effect size measures. For each index, the participants had to judge the magnitude of the shown effect, to indicate how certain they felt about their own answer and how useful they found the given effect size index. FINDINGS: Overall, 762 (57.9%) participants fully completed the questionnaire. In terms of understanding, the best results emerged when both the control event rate (CER) and the experimental event rate (EER) were presented. The difference in minimal importance difference units (MID unit) was understood worst. Respondents also found CER and EER to be the most useful presentation approach while they rated MID unit as the least useful. Confidence in the risk ratio ranked high, even though it was rather poorly understood. CONCLUSIONS AND CLINICAL IMPLICATIONS: For dichotomous outcomes, presenting the effects in terms of the CER and EER could lead to the most correct interpretation. Relative measures including the risk ratio must be supplemented with absolute measures such as the CER and EER. Effects on continuous outcomes were better understood through standardised mean differences than mean differences. These can also be supplemented by dichotomised CER and EER.

Components and Delivery Formats of Cognitive Behavioral Therapy for Chronic Insomnia in Adults: A Systematic Review and Component Network Meta-Analysis.

Importance: Chronic insomnia disorder is highly prevalent, disabling, and costly. Cognitive behavioral therapy for insomnia (CBT-I), comprising various educational, cognitive, and behavioral strategies delivered in various formats, is the recommended first-line treatment, but the effect of each component and delivery method remains unclear. Objective: To examine the association of each component and delivery format of CBT-I with outcomes. Data Sources: PubMed, Cochrane Central Register of Controlled Trials, PsycInfo, and International Clinical Trials Registry Platform from database inception to July 21, 2023. Study Selection: Published randomized clinical trials comparing any form of CBT-I against another or a control condition for chronic insomnia disorder in adults aged 18 years and older. Insomnia both with and without comorbidities was included. Concomitant treatments were allowed if equally distributed among arms. Data Extraction and Synthesis: Two independent reviewers identified components, extracted data, and assessed trial quality. Random-effects component network meta-analyses were performed. Main Outcomes and Measures: The primary outcome was treatment efficacy (remission defined as reaching a satisfactory state) posttreatment. Secondary outcomes included all-cause dropout, self-reported sleep continuity, and long-term remission. Results: A total of 241 trials were identified including 31 452 participants (mean [SD] age, 45.4 [16.6] years; 21 048 of 31 452 [67%] women). Results suggested that critical components of CBT-I are cognitive restructuring (remission incremental odds ratio [iOR], 1.68; 95% CI, 1.28-2.20) third-wave components (iOR, 1.49; 95% CI, 1.10-2.03), sleep restriction (iOR, 1.49; 95% CI, 1.04-2.13), and stimulus control (iOR, 1.43; 95% CI, 1.00-2.05). Sleep hygiene education was not essential (iOR, 1.01; 95% CI, 0.77-1.32), and relaxation procedures were found to be potentially counterproductive(iOR, 0.81; 95% CI, 0.64-1.02). In-person therapist-led programs were most beneficial (iOR, 1.83; 95% CI, 1.19-2.81). Cognitive restructuring, third-wave components, and in-person delivery were mainly associated with improved subjective sleep quality. Sleep restriction was associated with improved subjective sleep quality, sleep efficiency, and wake after sleep onset, and stimulus control with improved subjective sleep quality, sleep efficiency, and sleep latency. The most efficacious combination-consisting of cognitive restructuring, third wave, sleep restriction, and stimulus control in the in-person format-compared with in-person psychoeducation, was associated with an increase in the remission rate by a risk difference of 0.33 (95% CI, 0.23-0.43) and a number needed to treat of 3.0 (95% CI, 2.3-4.3), given the median observed control event rate of 0.14. Conclusions and Relevance: The findings suggest that beneficial CBT-I packages may include cognitive restructuring, third-wave components, sleep restriction, stimulus control, and in-person delivery but not relaxation. However, potential undetected interactions could undermine the conclusions. Further large-scale, well-designed trials are warranted to confirm the contribution of different treatment components in CBT-I.

Cognitive behavioral therapy for insomnia to treat major depressive disorder with comorbid insomnia: A systematic review and meta-analysis.

OBJECTIVE: Cognitive behavioral therapy for insomnia (CBT-I) has demonstrated efficacy for both insomnia and depression. With a tenfold increase in expected participant numbers, we aimed to update the systematic review and meta-analysis of CBT-I for major depressive disorders (MDD). METHODS: Multiple databases were searched up to March 27th 2024 to include all randomized controlled trials examining CBT-I among adults with MDD. The certainty of evidence was evaluated using GRADE. The primary outcome was depression response at post-treatment. Secondary outcomes included insomnia remission and all-cause dropout at post-treatment. Frequentist random-effects pairwise meta-analyses were performed using odds ratio (OR) for dichotomous outcomes. This study was prospectively registered (https://osf.io/kcndz/). RESULTS: Nineteen trials with 4808 randomized participants were identified (mean age, 33.2 [standardized deviation 15.0] years, 73.2 % women. Mean Insomnia Severity Index 19.2 [5.4], median Patient Health Questionnaire-9 16 [range, 8-21]). CBT-I was more beneficial than control conditions for depression response (OR 2.28 [95 % Confidence Interval (CI), 1.67-3.12; GRADE certainty of evidence: moderate), insomnia remission (OR 3.57 [95%CI, 2.48-5.14]: moderate) but could lead to more dropout (OR 1.69 [95%CI, 0.98-2.89]: low). Depression improvement was seen beyond the sleep domain. With a control condition depression response rate of 17 % at post-treatment (median 8 weeks), CBT-I yielded a 32 % response rate (95 % CI, 26 %-39 %). CONCLUSIONS: This meta-analysis indicates that CBT-I has significant effects on depressive symptoms beyond the sleep domain among people with MDD. Despite higher dropout rates, these findings suggest CBT-I is an effective treatment for depression comorbid with insomnia.

Transformation of metal-organic framework to polymer gel by cross-linking the organic ligands preorganized in metal-organic framework.

Until now, seamless fusion of metal-organic frameworks (MOFs) and covalently cross-linked polymer gels (PG) at molecular level has been extremely rare, since these two matters have been regarded as opposite, that is, hard versus soft. In this report, we demonstrate transformation of cubic MOF crystals to PG via inner cross-linking of the organic linkers in the void space of MOF, followed by decomposition of the metal coordination. The obtained PG behaved as a polyelectrolyte gel, indicating the high content of ionic groups inside. Metal ions were well adsorbed in the PG due to its densely packed carboxylate groups. A chimera-type hybrid material consisting of MOF and PG was obtained by partial hydrolysis of resulting cross-linked MOF. The shape of resulting PG network well reflected the crystal structure of MOF employed as a template. Our results will connect the two different network materials that have been ever studied in the two different fields to provide new soft and hard hybrid materials, and the unique copolymerization in the large void space of the MOF will open a new horizon toward "ideal network polymers" never prepared before now.

Diagnosis of a SMARCA4-deficient undifferentiated tumor using multigene panel testing: A case report.

Key Clinical Message: SMARCA4-deficient thoracic carcinoma is a malignant tumor that may present as cancer of unknown primary. This tumor is refractory and requires a novel approach. In addition to identifying therapeutic targets, multigene panel testing can reveal novel genetic mutations, leading to more pathologically relevant diagnoses and appropriate tumor care. Abstract: SMARCA4-deficient undifferentiated tumors are characterized by SMARCA4 inactivation. We present a case of a 74-year-old man with an undifferentiated tumor and a novel SMARCA4 mutation detected using multigene panel testing. The tumor was multiagent and refractory to three chemotherapy lines. The test results helped guide appropriate medical management.

Serological response 5 months after the BNT162b2 COVID-19 vaccination in patients with various hematological disorders in Japan.

Purpose: Patients with hematological malignancies are at an increased risk of severe infection with coronavirus disease 2019 (COVID-19). However, developing an adequate immune response after vaccination is difficult, especially in patients with lymphoid neoplasms. Since the long-term effects of the BNT162b2 vaccine are unclear, the humoral immune response 5 months after the two vaccinations in patients with hematological disorders was analyzed. Materials and Methods: Samples were collected from 96 patients vaccinated twice with BNT162b2 and treated with at least one line of an antitumor or immunosuppressive drug in our hospital from November 2021 to February 2022. Serum anti-severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) spike (S) antibody titers were analyzed. Patients were age- and sex-matched using propensity matching and compared with a healthy control group. Patients with serum anti-SARS-CoV-2 S antibodies were defined as 'responder' if >50 U/mL. The patients had B-cell non-Hodgkin lymphoma (B-NHL), multiple myeloma, chronic myeloid leukemia, etc. Results: Patients had significantly low antibody levels (median, 55.3 U/mL vs. 809.8 U/mL; p<0.001) and a significantly low response rate (p<0.001). Multivariate analysis showed that patients with B-NHL, aged >72 years, were associated with a low response to vaccination. There were no significant differences between patients with chronic myeloid leukemia and healthy controls. Conclusion: Our study shows that patients with hematological disorders are at risk of developing severe COVID-19 infections because of low responsiveness to vaccination. Moreover, the rate of antibody positivity differed between the disease groups. Further studies are warranted to determine an appropriate preventive method for these patients, especially those with B-NHL.

Optimal duration of antibiotic treatment for community-acquired pneumonia in adults: a systematic review and duration-effect meta-analysis.

OBJECTIVES: To find the optimal treatment duration with antibiotics for community-acquired pneumonia (CAP) in adults. DESIGN: Systematic review and duration-effect meta-analysis. DATA SOURCES: MEDLINE, Embase and CENTRAL through 25 August 2021. ELIGIBILITY CRITERIA: All randomised controlled trials comparing the same antibiotics used at the same daily dosage but for different durations for CAP in adults. Both outpatients and inpatients were included but not those admitted to intensive care units. We imposed no date, language or publication status restriction. DATA EXTRACTION AND SYNTHESIS: Data extraction by two independent reviewers. We conducted a random-effects, one-stage duration-effect meta-analysis with restricted cubic splines. We tested the non-inferiority with the prespecified non-inferiority margin of 10% examined against 10 days . The primary outcome was clinical improvement on day 15 (range 7-45 days). SECONDARY OUTCOMES: all-cause mortality, serious adverse events and clinical improvement on day 30 (15-60 days). RESULTS: We included nine trials (2399 patients with a mean (SD) age of 61.2 (22.1); 39% women). The duration-effect curve was monotonic with longer duration leading to a lower probability of improvement, and shorter treatment duration (3-9 days) was likely to be non-inferior to 10-day treatment. Harmful outcome curves indicated no association. The weighted average percentage of the primary outcome in the 10-day treatment arms was 68%. Using that average, the absolute clinical improvement rates of the following durations were: 3-day treatment 75% (95% CI: 68% to 81%), 5-day treatment 72% (95% CI: 66% to 78%) and 7-day treatment 69% (95% CI: 61% to 76%). CONCLUSIONS: Shorter treatment duration (3-5 days) probably offers the optimal balance between efficacy and treatment burden for treating CAP in adults if they achieved clinical stability. However, the small number of included studies and the overall moderate-to-high risk of bias may compromise the certainty of the results. Further research on the shorter duration range is required. PROSPERO REGISTRATION NUMBER: CRD 42021273357.

Nano- and microsized cubic gel particles from cyclodextrin metal-organic frameworks.

Sweet cube o' mine: Bottom-up control of gel particles has been regarded as a great challenge. By employing internal cross-linking of cyclodextrin metal-organic frameworks, cubic sugar gels were formed with sharp edges that reflect the shape of the crystals. This enabled the fabrication of shape- and size-controlled polymer gels from porous crystals (see picture).

Assessing the quality of cancer screening leaflets using the International Patient Decision Aids Standards instrument: A cross-sectional content analysis.

OBJECTIVE: To assess the quality of national cancer screening program leaflets in Japan from the informed-decision perspective. METHODS: Cross-sectional content analysis of invitation leaflets issued by centralized organizations and used nationwide in Japan was conducted. Three members independently evaluated the materials using International Patient Decision Aids Standards six-item minimum criteria for qualifying patient decision aids. PATIENT PUBLIC INVOLVEMENT: Co-author KH is a cancer patient himself. We also sought feedbacks from three other cancer survivors and two bereaved family members. RESULTS: Inter-rater agreement was substantial (Fleiss' kappa=0.62). The median score was 2 out of 6 (range: 2-3). All leaflets described the cancer (Q1: 7/7) and screening modality (Q2: 7/7). None stated not undergoing screening as an option. One stated another screening modality (Q3: 1/7). None stated both the positive and negative features of multiple options (Q4: 0/7. Q5: 0/7). One described the psychological and social experience of screening but only its positive side (Q6: 1/7). CONCLUSIONS: There is room for improvement in the content of the public cancer screening invitation leaflets in Japan from informed-decision perspective. PRACTICE IMPLICATIONS: Cancer screening leaflets should provide evidence-based, well-balanced, easy-to-understand information to educate people on cancer screening while maintaining people's autonomy.

Initial treatment choices to achieve sustained response in major depression: a systematic review and network meta-analysis.

Major depression is often a relapsing disorder. It is therefore important to start its treatment with therapies that maximize the chance of not only getting the patients well but also keeping them well. We examined the associations between initial treatments and sustained response by conducting a network meta-analysis of randomized controlled trials (RCTs) in which adult patients with major depression were randomized to acute treatment with a psychotherapy (PSY), a protocolized antidepressant pharmacotherapy (PHA), their combination (COM), standard treatment in primary or secondary care (STD), or pill placebo, and were then followed up through a maintenance phase. By design, acute phase treatment could be continued into the maintenance phase, switched to another treatment or followed by discretionary treatment. We included 81 RCTs, with 13,722 participants. Sustained response was defined as responding to the acute treatment and subsequently having no depressive relapse through the maintenance phase (mean duration: 42.2±16.2 weeks, range 24-104 weeks). We extracted the data reported at the time point closest to 12 months. COM resulted in more sustained response than PHA, both when these treatments were continued into the maintenance phase (OR=2.52, 95% CI: 1.66-3.85) and when they were followed by discretionary treatment (OR=1.80, 95% CI: 1.21-2.67). The same applied to COM in comparison with STD (OR=2.90, 95% CI: 1.68-5.01 when COM was continued into the maintenance phase; OR=1.97, 95% CI: 1.51-2.58 when COM was followed by discretionary treatment). PSY also kept the patients well more often than PHA, both when these treatments were continued into the maintenance phase (OR=1.53, 95% CI: 1.00-2.35) and when they were followed by discretionary treatment (OR=1.66, 95% CI: 1.13-2.44). The same applied to PSY compared with STD (OR=1.76, 95% CI: 0.97-3.21 when PSY was continued into the maintenance phase; OR=1.83, 95% CI: 1.20-2.78 when PSY was followed by discretionary treatment). Given the average sustained response rate of 29% on STD, the advantages of PSY or COM over PHA or STD translated into risk differences ranging from 12 to 16 percentage points. We conclude that PSY and COM have more enduring effects than PHA. Clinical guidelines on the initial treatment choice for depression may need to be updated accordingly.