Chloride reduces plant nitrate requirement and alleviates low nitrogen stress symptoms.

Chloride (Cl-) is traditionally categorized as an antagonist of nitrate (NO3-) because Cl- hinders plant NO3- transport and accumulation. However, we have recently defined Cl- as a beneficial macronutrient for higher plants, due to specific functions that lead to more efficient use of water, nitrogen (N) and CO2 under optimal N and water supply. When accumulated in leaves at macronutrient levels, Cl- promotes growth through osmotic, physiological, metabolic, anatomical and cellular changes that improve plant performance under optimal NO3- nutrition. Nitrate over-fertilization in agriculture can adversely affect crop yield and nature, while its deficiency limits plant growth. To study the relationship between Cl- nutrition and NO3- availability, we have characterized different physiological responses such as growth and yield, N-use efficiency, water status, photosynthesis, leaf anatomy, pigments and antioxidants in tomato plants treated with or without 5 mM Cl- salts and increasing NO3- treatments (3-15 mM). First, we have demonstrated that 5 mM Cl- application can reduce the use of NO3- in the nutrient solution by up to half without detriment to plant growth and yield in tomato and other horticultural plants. Second, Cl- application reduced stress symptoms and improved plant growth under low-NO3- conditions. The Cl--dependent resistance to low-N stress resulted from: more efficient use of the available NO3-; improved plant osmotic and water status regulation; improved stomatal conductance and photosynthetic rate; and better antioxidant response. We proposed that beneficial Cl- levels increase the crop ability to grow better with lower NO3- requirements and withstand N deficiency, promoting a more sustainable and resilient agriculture.

Analysis of diurnal variation in serum testosterone levels in men with symptoms of testosterone deficiency.

BACKGROUND: Testosterone (T) plays a crucial role in various physiological functions in men, and understanding the variations in T levels during the day is essential for diagnosing and treating testosterone deficiency (TD). AIM: We sought to evaluate the reduction in serum total T (TT) levels throughout the day in men with symptoms of testosterone deficiency and to determine the variables having an impact on the extent of this decline. METHODS: The study population consisted of a group of men who within 3 months of each other had all undergone both early morning and afternoon TT level measurements. We did not include patients with a history of a prior orchiectomy, testosterone levels below 100 ng/dL or above 1000 ng/dL, a history of androgen deprivation therapy, or patients on T therapy. Statistical analyses were conducted using descriptive statistics, t-tests, chi-square tests, and correlation calculations. Liquid chromatography-tandem mass spectrometry was used to measure TT, and a change in TT levels greater than 100 ng/dL was considered significant. Using multivariable and univariable analysis, we attempted to define predictors of a decrease in afternoon TT levels. OUTCOMES: The majority of men showed no significant difference in T levels between morning and afternoon. RESULTS: In total, 506 men with a median age of 65 years were analyzed. The most common comorbidities were hypertension and hyperlipidemia. Levels of TT were measured in the morning and afternoon, and no significant differences in mean T levels based on the time of the test were found. Age was not significantly associated with T levels. CLINICAL IMPLICATIONS: There was a weak negative correlation between age and the difference between morning and afternoon T levels, with younger men showing more significant variations in T levels. The most considerable differences in T levels were observed in men younger than 30 years. There were no predictors of the magnitude of the T decrease in the afternoon. STRENGTHS AND LIMITATIONS: Strengths of the study include the number of subjects and the use of liquid chromatography-tandem mass spectrometry for T measurement. Limitations include failure to measure morning and afternoon T levels on the same day, the retrospective nature of the study, and a smaller sample size of patients younger than 30 years. CONCLUSION: In this study we found no strong link between age and daily T fluctuation, but we observed a decrease in the magnitude of variation with aging. The group experiencing the most significant decline in daily T had higher morning and consistently normal afternoon T levels.

Do Phosphodiesterase Type 5 Inhibitors Increase the Risk of Biochemical Recurrence After Radical Prostatectomy?

PURPOSE: There have been conflicting studies on the association between phosphodiesterase type 5 inhibitor (PDE5i) use and biochemical recurrence (BCR) following radical prostatectomy (RP). Our aim was to determine whether PDE5i drug exposure after RP increases the risk of BCR in patients undergoing RP. MATERIALS AND METHODS: An institutional database of prostate cancer patients treated between January 2009 and December 2020 was reviewed. BCR was defined as 2 PSA measurements greater than 0.1 ng/mL. PDE5i exposure was defined using a 0 to 3 scale, with 0 representing never use, 1 sometimes use, 2 regularly use, and 3 routinely use. The risk of BCR with any PDE5i exposure, the quantity of exposure, and the duration of PDE5i exposure were assessed by multivariable Cox proportional hazards models. RESULTS: The sample size included 4630 patients to be analyzed, with 776 patients having BCR. The median follow-up for patients without BCR was 27 (IQR 12, 49) months. Eighty-nine percent reported taking a PDE5i at any time during the first 12 months after RP, and 60% reported doing so for 6 or more months during the year after RP. There was no evidence of an increase in the risk of BCR associated with any PDE5i use (HR 1.05, 95% CI 0.84, 1.31, P = .7) or duration of PDE5i use in the first year (HR 0.98 per 1 month duration, 95% CI 0.96, 1.00, P = .055). Baseline oncologic risk was lower in patients using PDE5i, but differences between groups were small, suggesting that residual confounding is unlikely to obscure any causal association with BCR. CONCLUSIONS: Prescription of PDE5i to men after RP can be based exclusively on quality of life considerations. Patients receiving PDE5is can be reassured that their use does not increase the risk of BCR.

Treatment Outcomes With Licensed and Unlicensed Stimulant Doses for Adults With Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-Analysis.

Importance: Stimulants (methylphenidate and amphetamines) are often prescribed at unlicensed doses for adults with attention-deficit/hyperactivity disorder (ADHD). Whether dose escalation beyond US Food and Drug Administration recommendations is associated with positive risk benefits is unclear. Objective: To investigate the impact, based on averages, of stimulant doses on treatment outcomes in adults with ADHD and to determine, based on averages, whether unlicensed doses are associated with positive risk benefits compared with licensed doses. Data Sources: Twelve databases, including published (PubMed, Cochrane Library, Embase, Web of Sciences) and unpublished (ClinicalTrials.gov) literature, up to February 22, 2023, without language restrictions. Study Selection: Two researchers independently screened records to identify double-blinded randomized clinical trials of stimulants against placebo in adults (18 years and older) with ADHD. Data Extraction and Synthesis: Aggregate data were extracted and synthesized in random-effects dose-response meta-analyses and network meta-analyses. Main Outcome Measures: Change in ADHD symptoms and discontinuations due to adverse events. Results: A total of 47 randomized clinical trials (7714 participants; mean age, 35 (SD, 11) years; 4204 male [56%]) were included. For methylphenidate, dose-response curves indicated additional reductions of symptoms with increments in doses, but the gains were progressively smaller and accompanied by continued additional risk of adverse events dropouts. Network meta-analyses showed that unlicensed doses were associated with greater reductions of symptoms compared with licensed doses (standardized mean difference [SMD], -0.23; 95% CI, -0.44 to -0.02; very low certainty of evidence), but the additional gain was small and accompanied by increased risk of adverse event dropouts (odds ratio, 2.02; 95% CI, 1.19-3.43; moderate certainty of evidence). For amphetamines, the dose-response curve approached a plateau and increments in doses did not indicate additional reductions of symptoms, but there were continued increments in the risk of adverse event dropouts. Network meta-analysis did not identify differences between unlicensed and licensed doses for reductions of symptoms (SMD, -0.08; 95% CI, -0.24 to 0.08; very low certainty of evidence). Conclusions and Relevance: Based on group averages, unlicensed doses of stimulants may not have positive risk benefits compared with licensed doses for adults with ADHD. In general, practitioners should consider unlicensed doses cautiously. Practitioners may trial unlicensed doses if needed and tolerated but should be aware that there may not be large gains in the response to the medication with those further increments in dose. However, the findings are averages and will not generalize to every patient.

Identifying robust adaptive irrigation operating policies to balance deeply uncertain economic food production and groundwater sustainability trade-offs.

Increasing irrigation demand has heavily relied on groundwater use, especially in places with highly variable water supplies that are vulnerable to drought. Groundwater management in agriculture is becoming increasingly challenging given the growing effects from overdraft and groundwater depletion worldwide. However, multiple challenges emerge when seeking to develop sustainable groundwater management in irrigated systems, such as trade-offs between the economic revenues from food production and groundwater resources, as well as the broad array of uncertainties in food-water systems. In this study we explore the applicability of Evolutionary Multi-Objective Direct Policy Search (EMODPS) to identify adaptive irrigation policies that water agencies and farmers can implement including operational decisions related to land use and groundwater use controls as well as groundwater pumping fees. The EMODPS framework yields state-aware, adaptive policies that respond dynamically as system state conditions change, for example with variable surface water (e.g., shifting management strategies across wet versus dry years). For this study, we focus on the Semitropic Water Storage district located in the San Joaquin Valley, California to provide broader insights relevant to ongoing efforts to improve groundwater sustainability in the state. Our findings demonstrate that adaptive irrigation policies can achieve sufficiently flexible groundwater management to acceptably balance revenue and sustainability goals across a wide range of uncertain future scenarios. Among the evaluated policy decisions, pumping restrictions and reductions in inflexible irrigation demands from tree crops are actions that can support dry-year pumping while maximizing groundwater storage recovery during wet years. Policies suggest that an adaptive pumping fee is the most flexible decision to control groundwater pumping and land use.

Pharmacological and Somatic Treatment Effects on Suicide in Adults: A Systematic Review and Meta-Analysis.

Background: Suicide is a public health crisis. We conducted a systematic review and meta-analysis of the effects of psychopharmacologic and somatic therapies on suicide risk. Methods: A systematic search of MEDLINE for studies evaluating the effects of pharmacologic (excluding antidepressants) or somatic interventions on suicide risk was conducted. Studies were included if they used a comparison group, reported on suicide death, assessed a psychopharmacological or somatic intervention, and included adults. Study quality was assessed using the Newcastle-Ottawa scale. Fifty-seven studies were included from 2940 reviewed citations. Results: In bipolar disorder, lithium was associated with a reduction in the odds of suicide compared to active controls (odds ratio [OR] = .58, p = .005; k = 12) and compared to placebo/no lithium (OR = .46, p = .009; k = 9). In mixed diagnostic samples, lithium was associated with a reduction in the odds of suicide compared to placebo/no lithium (OR = .27, p < .001; k = 12), but not compared to active controls (OR = .89, p = .468; k = 7). In psychotic disorders, clozapine was associated with a reduction in the odds of suicide (OR = .46, p = .007; k = 7). Associations between suicide death and electroconvulsive therapy (OR = .77, p = .053; k = 11), non-clozapine antipsychotics in bipolar disorder (OR = .73, p = .090; k = 6) and antipsychotics in psychotic disorders (OR = .39, p = .069; k = 6) were not significant. There was no consistent relationship between antiepileptic mood stabilizers and suicide. There were insufficient studies to meta-analyze associations of suicide risk with vagus nerve stimulation, transcranial magnetic stimulation, magnetic seizure therapy, or transcranial direct current stimulation. Conclusion: Lithium and clozapine have consistent data supporting protective effects against suicide in certain clinical contexts.Reprinted from Depress Anxiety 2022; 39:100-112, with permission from John Wiley and Sons. Copyright © 2022.

Characteristics of trichotillomania and excoriation disorder across the lifespan.

Trichotillomania (hair-pulling disorder) and excoriation (skin-picking) disorder are body-focused repetitive behaviors, which often first present in adolescence and cause distress and impairment into adulthood. Few studies have examined the clinical characteristics of the co-occurrence of these conditions across the lifespan. We examined cross-sectional survey responses collected from April 2018-February 2020 to evaluate the relationship between trichotillomania, excoriation disorder, and their co-occurrence. Responses from individuals with trichotillomania (n = 50), excoriation disorder (n = 52), and both conditions (n = 50) ages 4-67 years old were compared for co-occurring conditions and current symptoms. Self-report measures of hair-pulling and skin-picking severity and subtypes were assessed. Gender, race, and co-occurring conditions were generally similarly distributed across the three groups with high rates of self-reported anxiety (63-82%), depression (34-50%), obsessive-compulsive disorder (16-29%), and attention-deficit/hyperactivity disorder (12-32%). Among individuals with both trichotillomania and excoriation disorder, significant positive correlations were observed between hair-pulling and skin-picking severity scores as well as hair-pulling and skin-picking subtypes. Hair-pulling and skin-picking severity peaked at the transition from adolescence to adulthood and hair-pulling/skin-picking styles appeared to shift across the lifespan. Our results support several similarities between trichotillomania and excoriation disorder, providing new insight into the clinical characteristics of these conditions.

Systematic review and meta-analysis: Season of birth and schizophrenia risk.

OBJECTIVE: Winter birth has been hypothesized to be associated with increased schizophrenia risk for nearly a century. Major hypotheses regarding the potential etiological risk factors for schizophrenia such as vitamin D deficiency and virus exposure in utero are predicated based on the observation that risk of schizophrenia is higher in children born in winter months. METHODS: We conducted a systematic review and meta-analysis to examine the association between season and month of birth and risk of schizophrenia. We further investigated this relationship stratified by hemisphere. RESULTS: Forty-three studies spanning 30 countries and territories and 440,039 individuals with schizophrenia were included in this meta-analysis. Winter births were associated with a small but statistically significant increased risk of schizophrenia (OR 1.05, 95 % CI 1.03-1.07, p < 0.0001) and summer births were associated with a small but statistically significant decreased risk of schizophrenia (OR 0.96, 95 % CI 0.94-0.98, p = 0.0001). Stratified subgroup analysis demonstrated no significant difference between hemispheres in the risk of schizophrenia for either winter or summer births. CONCLUSIONS: Analysis using birth month data demonstrated a clear seasonal trend towards increased risk of schizophrenia being associated with winter birth months and decreased risk of schizophrenia in summer-to-fall months in the Northern but not Southern Hemisphere. These data suggest a small-but-substantial increased risk of schizophrenia in winter birth month. Further research needs to examine potential etiologic causes for this association.

Association Between Patient Race and Ethnicity and Outcomes With COVID-19: A Retrospective Analysis From a Large Mid-Atlantic Health System.

BACKGROUND: Members of racial and ethnic minority groups have been disproportionately impacted by coronavirus-2019 (COVID-19). The objective of the study is to describe associations between race and ethnicity on clinical outcomes such as need for mechanical ventilation and mortality. METHODS: Retrospective cohort study of patients with severe COVID-19 infection admitted within a large, not-for-profit healthcare system in the mid-Atlantic region between March and July, 2020. Patient demographic data and clinical outcomes were abstracted from the electronic health record. Logistic regressions were performed to estimate associations between race and ethnicity and the clinical outcomes. RESULTS: The study population (N = 2931) was stratified into 1 of 3 subgroups: non-Hispanic White (n = 466), non-Hispanic Black (n = 1611), and Hispanic (n = 654). The average age of White, Black, and Hispanic patients was 69 ± 17.06, 64 ± 15.9, and 50 ± 15.53 years old, respectively (P < .001). Compared to White patients, Black and Hispanic patients were at increased odds of needing mechanical ventilation due to COVID-19 pneumonia (odds ratio [OR] Black = 1.35, 95% confidence interval [CI] = 1.04 to 1.75, P < .05; OR Hispanic = 1.43, 95% CI = 1.06 to 1.93, P < .05). When compared to White patients, Hispanic patients were at decreased odds of death (OR = 0.45, 95% CI = 0.32 to 0.63, P < .001). However, when adjusting for age, there were no statistically significant differences in the odds of death between these groups (adjusted OR [aOR] Black = 1.05, 95% CI = 0.80 to 1.38, P = .71; aOR Hispanic = 1.10, 95% CI = 0.76 to 1.60, P = .62). CONCLUSION: Our analysis demonstrated that Hispanic patients were more likely require mechanical ventilation but had lower mortality when compared to White patients, with lower average age likely mediating this association. These findings emphasize the importance of outreach efforts to communities of color to increase prevention measures and vaccination uptake to reduce infection with COVID-19.

Water, environment, and socioeconomic justice in California: A multi-benefit cropland repurposing framework.

Low-income, rural frontline communities of California's Central Valley experience environmental and socioeconomic injustice, water insecurity, extremely poor air quality, and lack of fundamental infrastructure (sewage, green areas, health services), which makes them less resilient. Many communities depend financially on agriculture, while water scarcity and associated policy may trigger farmland retirement further hindering socioeconomic opportunities. Here we propose a multi-benefit framework to repurpose cropland in buffers inside and around (400-m and 1600-m buffers) 154 rural disadvantaged communities of the Central Valley to promote socioeconomic opportunities, environmental benefits, and business diversification. We estimate the potential for (1) reductions in water and pesticide use, nitrogen leaching, and nitrogen gas emissions, (2) managed aquifer recharge, and (3) economic and employment impacts associated with clean industries and solar energy. Retiring cropland within 1600-m buffers can result in reductions in water use of 2.18 km3/year, nitrate leaching into local aquifers of 105,500 t/year, greenhouse gas emissions of 2,232,000 t CO2-equivalent/year, and 5388 t pesticides/year, with accompanying losses in agricultural revenue of US$4213 million/year and employment of 25,682 positions. Buffer repurposing investments of US$27 million/year per community for ten years show potential to generate US$101 million/year per community (total US$15,578 million/year) for 30 years and 407 new jobs/year (total 62,697 jobs/year) paying 67 % more than prior farmworker jobs. In the San Joaquin Valley (southern Central Valley), where groundwater overdraft averages 2.3 km3/year, potential water use reduction is 1.8 km3/year. We have identified 99 communities with surficial soils adequate for aquifer recharge and canals/rivers within 1600 m. This demonstrates the potential of managed aquifer recharge in buffered zones to substantially reduce overdraft. The buffers framework shows that well-planned land repurposing near disadvantaged communities can create multiple benefits for farmers and industry stakeholders, while improving quality of life in disadvantaged communities and producing positive externalities for society.

Avoidant/resistant rather than tolerant olive rootstocks are more effective in controlling Verticillium wilt.

The identification of rootstocks of low susceptibility to Verticillium dahliae can become a valuable procedure to achieve effective control of Verticillium wilt in the olive grove. This not only involves the identification of suitable genotypes, but also the study of the interaction between the rootstock and the grafted scion. Thus, a rootstock that prevents or minimizes V. dahliae proliferation (avoidance/resistance strategy) can have very different effects on a susceptible scion compared to a rootstock that shows few or no symptoms despite being infected (tolerance strategy). Both resistance and tolerance mechanisms have been recently identified in wild olive genotypes with low susceptibility to V. dahliae. When used as rootstocks of the highly susceptible variety 'Picual', we found that resistant genotypes, including the cultivar 'Frantoio', were more effective than tolerant genotypes in controlling Verticillium wilt. Furthermore, tolerant genotypes were as ineffective as susceptible or extremely susceptible genotypes in controlling Verticillium wilt. We also identified rootstock-scion combinations with behaviours that were not expected according to the degree of susceptibility previously observed in the non-grafted rootstock. Although the rootstocks were able to control Verticillium wilt according to its degree of susceptibility to V. dahliae, the ability to control the infection was not adequately transferred to the grafted scion. Our results confirmed that: the degree of susceptibility to Verticillium wilt of an olive variety does not predict its performance as a rootstock; to use a very low susceptible genotype as rootstock of a susceptible scion increases the susceptibility of the genotype used as rootstock; in any case, avoidant/resistant rootstocks are more effective than tolerant rootstocks in reducing the susceptibility of the grafted plant to V. dahliae.

Sexual Orientation and Racial Bias in Relation to Medical Specialty.

Physician explicit and implicit biases involving race and sexual orientation (SO) affect patient and provider experiences in healthcare settings. An anonymous survey was disseminated nationally to graduating medical students, residents, and practicing physicians to evaluate SO and racial biases across medical specialties. SO explicit and implicit bias were measured with the Attitudes toward Lesbians and Gay Men Scale, short form (ATLG-S) and Gay-Straight Implicit Association Test (IAT). Racial explicit and implicit bias were measured with the Quick Discrimination Index (QDI) and the Black-White IAT. Medical specialty was associated with racial explicit bias and specialty prestige with Black-White IAT score. Medical specialty and specialty prestige were not associated with SO bias. Female sex, sexual and gender minority (SGM) identity, and decreased religiosity were associated with reduced SO and racial bias. Provider race was associated with racial implicit and explicit bias.

A Randomized Multi-institutional Phase II Trial of Everolimus as Adjuvant Therapy in Patients with Locally Advanced Squamous Cell Cancer of the Head and Neck.

PURPOSE: Investigate whether adjuvant everolimus, an mTOR inhibitor, improves progression-free survival (PFS) in advanced-stage head and neck squamous cell carcinoma (HNSCC) and provide outcomes related to correlative biological factors associated with disease control. PATIENTS AND METHODS: This was a prospective, randomized, double-blind phase II trial of patients with advanced-stage HNSCC from 13 institutions who were confirmed disease-free post-definitive therapy and enrolled between December 2010 and March 2015. Patients received adjuvant everolimus or placebo daily (10 mg, oral) for a maximum of 1 year. p16 IHC as a surrogate marker for human papillomavirus infection and whole-exome sequencing were performed. Cox proportional hazard models estimated hazard rates. Log-rank tests evaluated differences in survival. The primary endpoint was PFS. Secondary endpoints and objectives included overall survival (OS) and toxicity assessment. RESULTS: 52 patients [median (range) age, 58 (37-76) years; 43 men (83%), 9 women (17%)] were randomized to placebo (n = 24) or everolimus (n = 28). PFS favored everolimus, but was not significant [log-rank P = 0.093; HR = 0.44; 95% confidence interval (CI), 0.17-1.17]. There was no difference in OS (P = 0.29; HR = 0.57; 95% CI, 0.20-16.2). Everolimus resulted in significant improvement in PFS for p16-negative patients (n = 31; P = 0.031; HR = 0.26; 95% CI, 0.07-0.97), although subgroup analysis showed no difference for p16-positive patients (n = 21; P = 0.93). Further, PFS was significantly higher in TP53-mutated (TP53mut) patients treated with everolimus compared with placebo (log-rank P = 0.027; HR = 0.24; 95% CI, 0.06-0.95). No treatment difference was seen in patients with TP53 wild-type tumors (P = 0.79). CONCLUSIONS: p16-negative and TP53mut patients may benefit from adjuvant treatment with everolimus.

Predictors of Curvature Improvement in Men With Peyronie's Disease Treated With Intralesional Collagenase Clostridium Histolyticum.

INTRODUCTION: Penile curvature is the most common abnormality that is observed by men with Peyronie's disease (PD). Collagenase Clostridium histolyticum (CCH) has become a standard treatment for PD patients. AIM: To identify predictor factors associated with improvements of penile curvature outcomes in men with PD treated with CCH. METHODS: We retrospectively collected the data of patients with PD treated with CCH up to 8 injections divided into 4 cycles between January 2014 and July 2020. Per protocol, penile curvature was assessed at baseline, and after the second and ford CCH cycle. If after cycle 2, curvature demonstrated no improvement, or penile curvature was significantly improved and the patient was happy, no further treatment was recommended. However, if penile curvature was significantly improved and the patient remained dissatisfied, 4 cycles were completed. Three categories of response were evaluated: improvement (≥10 degrees or ≥20%, either 1 happens), unchanged (±10 degrees or ±20%) or worsened (≥10 degrees or ≥20%, either 1 happens). Logistic regression analyses were performed to evaluate predictive factors associated with penile curvature improvements. OUTCOMES: Degrees of the curvature changes between the baseline and after the cycles of CCH. RESULTS: A total of 114 patients underwent CCH treatment. Median age was 57 years. Median PD duration was 11 months. At baseline, mean curvature was 47 degrees, 65% had dorsal curvature, 53% mid-shaft location, and 15% calcification. After CCH treatment, the mean final curvature was 40 degrees. A total of 44% improved the curvature, 39% had no change while 17% worsened after CCH treatment. Of men who had penile curvature improvement with CCH treatment, the mean curvature decreasing in degrees and percentage were 22 degrees and 41%, respectively. Men with baseline curvature ≤ 30, 31-59, and ≥ 60 degrees, the percentage curvature improvement were 29%, 43%, and 60%, respectively. Baseline curvature was the only significant predictor of penile curvature improvement after CCH (OR 1.33, 95% CI = 1.1, 1.7). CLINICAL IMPLICATIONS: We confirmed baseline penile curvature is the most important predictive factor, and this is the first report describing proportions of penile curvature improvement with CCH treatment. STRENGTHS AND LIMITATIONS: This study has several strengths, including the use of validated instruments. Nonetheless, there are limitations: the retrospective nature of the study, a single institution; and modelling device was not controlled. CONCLUSION: Penile curvature improvement was significantly more common in patients with greater baseline curvature, reaching up to 60% for patients with ≥ 60 degrees. Flores JM, Nascimento B, Punjani N, et al. Predictors of Curvature Improvement in Men With Peyronie's Disease Treated With Intralesional Collagenase Clostridium Histolyticum. J Sex Med 2022;19:1680-1686.

The Relationship Between PSA and Total Testosterone Levels in Men With Prostate Cancer.

BACKGROUND: Prostate-specific antigen (PSA) secretion is a testosterone (T) dependent process. Published data suggest that a low T level is an independent predictor of higher-grade prostate cancer (PC). AIM: To evaluate the relationship between T and PSA in patients with PC. METHODS: All men diagnosed with PC with a recorded pre-treatment total T level measurement were included in this analysis. We analyzed demographic, clinical, and pathological data. Patients were stratified according to pretreatment PSA levels: <2 ng/mL, 2-4 ng/mL, >4 ng/mL. Low T was defined as total T < 10.4 nmol/L (300 ng/dL), very low T < 6.9 nmol/L (200 ng/dL). OUTCOMES: T levels by PSA groups according to the PC pathology. RESULTS: In this retrospective study, mean patient age was 61 years among 646 men. The distribution by PSA group was: 8% (<2), 17% (2-4), and 76% (>4). The mean T level across the entire cohort was 13 nmol/L (374 ng/dL). Overall, 30% had a T level < 10.4 nmol/L (300 ng/dL). The mean total T level by PSA group was: <2 ng/mL, 7 nmol/L (206 ng/dL); 2-4 ng/mL, 13 nmol/L (362 ng/dL); >4 ng/mL, 14 nmol/L (393 ng/dL), P < .001. PSA <4 ng/mL was a significant predictor of low T in men with PC GS ≥8. PSA <2 ng/mL was a significant predictor of very low T independent of the PC pathology. CLINICAL IMPLICATIONS: These findings suggest that clinicians should consider measuring T levels when a patient diagnosed with PC GS ≥8 and PSA level <4 ng/mL, and for each patient with PSA level <2 ng/mL independent of the PC pathology. STRENGTHS & LIMITATIONS: Our study has several strengths including (i) inclusion of a large population of men, (ii) use of a database which is audited and reviewed for accuracy annually, and (iii) use of an accurate T assay (LCMS). Nonetheless, there are limitations: (i) the subjects of the study are from a single institution, and (ii) we did not measure free T levels. CONCLUSION: In men with PC with GS ≥8, PSA level <4 ng/mL predicts low T. PSA <2 ng/mL predicts very low T independent of the PC pathology. Flores JM, Bernie HL, Miranda E, et al. The Relationship Between PSA and Total Testosterone Levels in Men With Prostate Cancer. J Sex Med 2022;19:471-478.

Characteristics of Assaultive Patients Whom Inpatient Psychiatric Staff Report to Law Enforcement.

OBJECTIVE: The authors sought to identify factors that affect hospital staff's decision to pursue criminal charges against patients who assault staff on inpatient psychiatric units. METHODS: Data on assaults occurring on inpatient psychiatric units in one hospital system were collected over 32 months, from November 1, 2016, to July 1, 2019. The events were grouped by whether staff pursued criminal charges after the incident. Descriptive statistics and regression models were used to describe the data and identify predictive variables. RESULTS: Data were reviewed from 9,654 admissions, of which 124 patient encounters involved assaults on staff. Overall, 27 (22%) of 124 assaults on staff resulted in staff pursuing criminal charges. Regression models indicated that criminal history (odds ratio [OR]=2.18, 95% CI=1.26-3.78, p=0.006), age (OR=0.92, 95% CI=0.91-0.94, p<0.001), and diagnosis of chronic mental illness with psychotic symptoms (OR=7.23, 95% CI=1.49-35.04, p=0.01) predicted patient assaults resulting in contact with law enforcement. Several variables were not statistically significantly associated with filing of criminal charges, including race, gender, degree of injury from the assault, number of instances of restraint, and number of as-needed medications. CONCLUSIONS: This is the largest quantitative study to examine the demographic and clinical factors that may play a role in whether staff pursue criminal charges against patients on inpatient psychiatric units. The results suggest that certain patients are more likely to be reported to law enforcement. Institutions should monitor factors that increase the likelihood of assaults on staff resulting in criminal charges and create policies that mitigate discrepancies in criminal justice involvement.

The effects of stimulant dose and dosing strategy on treatment outcomes in attention-deficit/hyperactivity disorder in children and adolescents: a meta-analysis.

Clinical guidelines currently recommend practitioners titrate stimulant medications, i.e., methylphenidate (MPH) and amphetamines (AMP), to the dose that maximizes symptom control without eliciting intolerable adverse events (AEs) when treating attention-deficit/hyperactivity disorder (ADHD) in school-aged children/adolescents. However, robust evidence-base regarding the effects of doses and dosing strategies of stimulants on clinical outcomes in the treatment of children/adolescents with ADHD is currently lacking and stimulants are often underdosed in clinical practice. To address this gap and provide rigorous evidence-base in relation to the dose and dosing strategy of stimulants, we conducted the largest systematic review and dose-response meta-analysis examining change in ADHD symptoms (efficacy), and treatment discontinuations due to AEs (tolerability) and any reason (acceptability). We conducted one-stage random-effects dose-response meta-analyses examining MPH and AMP separately, stratifying trials based on fixed-dose and flexible-dose design. Daily doses of stimulants were converted to MPH- and AMP-equivalent doses by adjusting for different pharmacokinetics across formulations. We also conducted pairwise meta-analyses to provide indirect comparisons between flexible-dose versus fixed-dose trials. Our study included 65 RCTs involving 7 877 children/adolescents. Meta-analyses of fixed-dose trials for both MPH and AMP demonstrated increased efficacy and increased likelihood of discontinuation due to AEs with increasing doses of stimulants. The incremental benefits of stimulants in terms of efficacy decreased beyond 30 mg of MPH or 20 mg of AMP in fixed-dosed trials. In contrast, meta-analyses of flexible-dose trials for both MPH and AMP demonstrated increased efficacy and reduced likelihood of discontinuations for any reason with increasing stimulant doses. The incremental benefits of stimulants in terms of efficacy remained constant across the FDA-licensed dose range for MPH and AMP in flexible-dose trials. Our results suggest that flexible titration as needed, i.e., considering the presence of ADHD symptoms, and tolerated, i.e., considering the presence of dose-limiting AEs, to higher doses of stimulants is associated with both improved efficacy and acceptability because practitioners can increase/reduce doses based on control of ADHD symptoms/dose-limiting AEs. Although fixed-dose trials that are required by the FDA are valuable to characterize dose-dependency, they may underestimate the true potential benefit of trialing dose-increases of stimulants in clinical practice by not allowing dose adjustment based on response and tolerability. Additional research is required to investigate potential long-term effects of using high doses of stimulants in clinical practice.