A revisited history of cacao domestication in pre-Columbian times revealed by archaeogenomic approaches.

Humans have a long history of transporting and trading plants, contributing to the evolution of domesticated plants. Theobroma cacao originated in the Neotropics from South America. However, little is known about its domestication and use in these regions. In this study, ceramic residues from a large sample of pre-Columbian cultures from South and Central America were analyzed using archaeogenomic and biochemical approaches. Here we show, for the first time, the widespread use of cacao in South America out of its native Amazonian area of origin, extending back 5000 years, likely supported by cultural interactions between the Amazon and the Pacific coast. We observed that strong genetic mixing between geographically distant cacao populations occurred as early as the middle Holocene, in South America, driven by humans, favoring the adaptation of T. cacao to new environments. This complex history of cacao domestication is the basis of today's cacao tree populations and its knowledge can help us better manage their genetic resources.

In-patient evolution of a high-persister Escherichia coli strain with reduced in vivo antibiotic susceptibility.

Gram-negative bacterial bloodstream infections (GNB-BSI) are common and frequently lethal. Despite appropriate antibiotic treatment, relapse of GNB-BSI with the same bacterial strain is common and associated with poor clinical outcomes and high healthcare costs. The role of persister cells, which are sub-populations of bacteria that survive for prolonged periods in the presence of bactericidal antibiotics, in relapse of GNB-BSI is unclear. Using a cohort of patients with relapsed GNB-BSI, we aimed to determine how the pathogen evolves within the patient between the initial and subsequent episodes of GNB-BSI and how these changes impact persistence. Using Escherichia coli clinical bloodstream isolate pairs (initial and relapse isolates) from patients with relapsed GNB-BSI, we found that 4/11 (36%) of the relapse isolates displayed a significant increase in persisters cells relative to the initial bloodstream infection isolate. In the relapsed E. coli strain with the greatest increase in persisters (100-fold relative to initial isolate), we determined that the increase was due to a loss-of-function mutation in the ptsI gene encoding Enzyme I of the phosphoenolpyruvate phosphotransferase system. The ptsI mutant was equally virulent in a murine bacteremia infection model but exhibited 10-fold increased survival to antibiotic treatment. This work addresses the controversy regarding the clinical relevance of persister formation by providing compelling data that not only do high-persister mutations arise during bloodstream infection in humans but also that these mutants display increased survival to antibiotic challenge in vivo.

The prevalence and severity of loneliness and deficits in perceived social support among who have received a 'personality disorder' diagnosis or have relevant traits: a systematic review.

BACKGROUND: Loneliness and struggles with unmet social needs are a common experience among people with 'personality disorder' diagnoses/traits. Given the impact of loneliness and poor perceived social support on mental health, and the importance of a sense of belonging for recovery, a systematic review examining the prevalence/severity of loneliness and deficits in perceived social support among people with 'personality disorder' diagnoses/traits is an essential step towards developing an intervention targeting the social needs of people with diagnoses/traits 'personality disorder'. Despite an extensive literature on loneliness and deficits of perceived social support among people with 'personality disorder' diagnosis/traits, to date there has been no systematic review of this evidence. METHOD: We conducted a systematic review synthesising quantitative data on the prevalence/severity of loneliness and deficits of perceived social support among people with diagnoses/traits of 'personality disorder' in comparison with other clinical groups and the general population. We searched Medline, Embase, PsycINFO, Web of Social Science, Google scholar and Ethos British Library from inception to December 2021. We conducted quality appraisals using the Joanna Briggs Critical appraisal tools and rated the certainty of evidence using the Grading of Recommendation, Assessment, Development and Evaluation approach. A narrative synthesis was used describing the direction and strength of associations prioritising high quality studies. FINDINGS: A final set of 70 studies are included in this review, most of which are cross-sectional studies (n = 55), based in the United States (51%) and focused on community samples. Our synthesis of evidence found that, across all types of 'personality disorders' (except 'narcissistic personality' traits), people with traits associated with 'personality disorder' or meeting criteria for a diagnosis of 'personality disorder', have higher levels of loneliness, lower perceived relationship satisfaction, and poorer social support than the general population or other clinical samples. CONCLUSION: The quality of evidence is judged as low quality. However, given the distressing nature of loneliness and the known negative effects of loneliness on mental health and recovery, it is important for future research to explore mechanisms by which loneliness may exacerbate 'personality disorder' symptoms and the impact this has on recovery.

Attitudes toward and experiences of clinical and non-clinical services among individuals who self-harm or attempt suicide: a systematic review.

The prevalence of self-harm has increased substantially in recent decades. Despite the development of guidelines for better management and prevention of self-harm, service users report that quality of care remains variable. A previous systematic review of research published to June 2006 documented largely negative experiences of clinical services among patients who self-harm. This systematic review summarized the literature published since then to July 2022 to examine contemporary attitudes toward and experience of clinical and non-clinical services among individuals who self-harm and their relatives. We systematically searched for literature using seven databases. Quality of studies was assessed using the Mixed-Methods Appraisal Tool and findings were summarized using a narrative synthesis. We identified 29 studies that met our inclusion criteria, all of which were from high- or middle-income countries and were generally of high methodological quality. Our narrative synthesis identified negative attitudes toward clinical management and organizational barriers across services. Generally, more positive attitudes were found toward non-clinical services providing therapeutic contact, such as voluntary sector organizations and social services, than clinical services, such as emergency departments and inpatient units. Views suggested that negative experiences of service provision may perpetuate a cycle of self-harm. Our review suggests that in recent years there has been little improvement in attitudes toward and experiences of services for patients who self-harm. These findings should be used to reform clinical guidelines and staff training across clinical services to promote patient-centered and compassionate care and deliver more effective, acceptable and accessible services.

Micronutrient intake from three popular diet patterns in the United States: modeled replacement of foods highest in added sugar and sodium using the National Health and Nutrition Examination Survey, 2005-2018.

Introduction: Fifty-two percent of adults in the United States reported following a popular diet pattern in 2022, yet there is limited information on daily micronutrient intakes associated with these diet patterns. The objective of the present study was to model the impact on micronutrient intake when foods highest in added sugar and sodium were replaced with healthier alternatives to align with the Dietary Guidelines for Americans recommendations. Methods: Dietary data were acquired from 34,411 adults ≥ 20 y in the National Health and Nutrition Examination Survey, 2005-2018. The National Cancer Institute methodology was used to estimate usual dietary intake at baseline of 17 micronutrients using information from up to two dietary recalls per person. A food substitution model was used to evaluate the impact on micronutrient intake when three servings of foods highest in added sugar and sodium were substituted with healthier alternatives. Results: Dietary modeling to replace foods highest in added sugar with healthier alternatives increased the mean intake of fat-soluble vitamins (0.15% for vitamin A to 4.28% for vitamin K), most water-soluble vitamins (0.01% for vitamin B1 to 12.09% for vitamin C), and most minerals (0.01% for sodium to 4.44% for potassium) across all diet patterns. Replacing foods highest in sodium had mixed effects on the mean intake of micronutrients. The intake of most fatsoluble vitamins increased by 1.37-6.53% (particularly vitamin A and D), yet while the intake of some water-soluble vitamins and minerals increased by 0.18-2.64% (particularly vitamin B2, calcium, and iron) others decreased by 0.56-10.38% (notably vitamin B3 and B6, magnesium, sodium, and potassium). Discussion: Modeled replacement of foods highest in added sugar led to more favorable changes in mean micronutrient intake compared to modeled replacement of foods highest in sodium. Due to the composite nature of mixed dishes that include multiple ingredients, food substitutions may result in both favorable and unfavorable changes in micronutrient intake. These findings highlight the challenges of making singleitem food substitutions to increase micronutrient intake and call for further research to evaluate optimal combinations of replacement foods to maximize the intake of all micronutrients simultaneously.

Effectiveness of nutrition counseling for pregnant women in low- and middle-income countries to improve maternal and infant behavioral, nutritional, and health outcomes: A systematic review.

Background: Nutritional counseling, which includes two-way interactive education, has been hypothesized to improve the health and nutritional status of pregnant women, but little is known about the impact such practice of care might have on maternal and infant health and behavioral outcomes of pregnant women living in low income, low-middle income, and upper-middle-income countries (LMIC)s. Objectives: We conducted a systematic review to appraise the effectiveness and impact on health equity of two-way nutritional counseling practices in LMICs on maternal and infant behavioral, nutritional, and health outcomes. Search Methods: We conducted electronic searches for relevant studies on Medline, Embase, CINAHL, PsychInfo, and the Cochrane CENTRAL for randomized and non-randomized trials on the effectiveness of two-way interactive nutritional counseling among pregnant women from the date of database inception up to June 22, 2021. In addition, we searched references of included studies in systematic reviews, gray literature resources, and unpublished studies or reports that satisfied our eligibility criteria using a focused Google search. Selection Criteria: We included randomized and non-randomized controlled studies (NRS), controlled before and after, and interrupted time series that assessed the effectiveness of two-way interactive nutrition counseling targeting pregnant women in LMICs. Data Collection and Analysis: Data extraction and risk of bias were conducted in duplicate. The risk of bias (ROB) for randomized trials (RCT) was assessed according to the Cochrane Handbook of Systematic Reviews, and ROB for NRS was assessed using the Newcastle-Ottawa scale (NOS). RCT and NRS were meta-analyzed separately. Main Results: Our search identified 6418 records and 52 studies met our inclusion criteria, but only 28 were used in the quantitative analysis. Twenty-eight studies were conducted in Asia, the most in Iran. Eight studies were conducted in Africa. Two-way interactive nutritional counseling during pregnancy may improve dietary caloric intake (mean difference [MD]: 81.65 calories, 95% confidence interval [CI], 15.37-147.93, three RCTs; I 2 = 42%; moderate certainty of evidence using GRADE assessment), may reduce hemorrhage (relative risk [RR]: 0.63; 95% CI, 0.25-1.54, two RCTs; I 2 = 40%; very low certainty of evidence using GRADE assessment), may improve protein (MD: 10.44 g, 95% CI, 1.83-19.05, two RCTs; I 2 = 95%; high certainty of evidence using GRADE assessment), fat intake (MD: 3.42 g, 95% CI, -0.20 to 7.04, two RCTs; I 2 = 0%; high certainty of evidence using GRADE assessment), and may improve gestational weight gain within recommendations (RR: 1.84; 95% CI, 1.10-3.09, three RCTs; I 2 = 69%). Nutrition counseling probably leads to the initiation of breastfeeding immediately after birth (RR: 1.72; 95% CI, 1.42-2.09, one RCT). There was little to no effect on reducing anemia (RR: 0.77; 95% CI, 0.50-1.20, three RCTs; I 2 = 67%; very low certainty of evidence using GRADE assessment) risk of stillbirths (RR: 0.81; 95% CI, 0.52-1.27, three RCTs; I 2 = 0%; moderate certainty of evidence using GRADE assessment) and risk of cesarean section delivery (RR: 0.96; 95% CI, 0.76-1.20, four RCTs; I 2 = 36%; moderate certainty of evidence using GRADE assessment). Authors' Conclusions: Our review highlights improvements in maternal behavioral and health outcomes through interactive nutrition counseling during pregnancy. However, we are uncertain about the effects of nutrition counseling due to the low certainty of evidence and a low number of studies for some key outcomes. Moreover, the effects on health equity remain unknown. More methodologically rigorous trials that focus on a precise selection of outcomes driven by the theory of change of nutrition counseling to improve maternal and infant behavioral and health outcomes and consider equity are required.

Long-term Dalbavancin for Suppression of Gram-Positive Chronic Left Ventricular Assist Device Infections.

Background: Infection is the leading cause of morbidity and mortality in patients with left ventricular assist devices (LVADs). Prolonged suppressive therapy should be strongly considered and is often used in patients with recurrent infections when source control cannot be achieved. Dalbavancin is a promising option in patients with LVADs requiring prolonged durations of antibiotic therapy, especially when no oral alternatives are available. Methods: This case series included 8 patients receiving dalbavancin for the long-term suppression of gram-positive infections at Emory University Hospital and Emory St Joseph's Hospital. Results: The overall incidence of breakthrough infections occurred in 5 of the 8 patients included in the study. One patient experienced an early breakthrough infection within 1 month of dalbavancin initiation. Another experienced a breakthrough infection within 3 and 6 months of dalbavancin initiation, and the final 3 patients experienced a breakthrough infection within 6 and 12 months. The average duration of dalbavancin suppression therapy among all patients was 229 days, and no adverse effects were reported. Conclusions: Dalbavancin is a promising option in patients who require long-term suppression for chronic gram-positive LVAD infections, given its unique pharmacokinetic profile and excellent tissue penetration. The use of biweekly dalbavancin infusions in our 8 patients prevented infection for an extended period of time despite some of the patients not being able to consistently receive infusions. Larger studies are needed to determine the efficacy and safety of using dalbavancin for long-term suppression of gram-positive LVAD infections.

Inflammasome-mediated glucose limitation induces antibiotic tolerance in Staphylococcus aureus.

Staphylococcus aureus is a leading human pathogen that frequently causes relapsing infections. The failure of antibiotics to eradicate infection contributes to infection relapse. Host-pathogen interactions have a substantial impact on antibiotic susceptibility and the formation of antibiotic tolerant cells. In this study, we interrogate how a major S. aureus virulence factor, α-toxin, interacts with macrophages to alter the microenvironment of the pathogen, thereby influencing its susceptibility to antibiotics. We find α-toxin-mediated activation of the NLRP3 inflammasome induces antibiotic tolerance. Induction of tolerance is driven by increased glycolysis in the host cells, resulting in glucose limitation and ATP depletion in S. aureus. Additionally, inhibition of NLRP3 activation improves antibiotic efficacy in vitro and in vivo, suggesting that this strategy has potential as a host-directed therapeutic to improve outcomes. Our findings identify interactions between S. aureus and the host that result in metabolic crosstalk that can determine the outcome of antimicrobial therapy.

Hydrogen Peroxide, Povidone-Iodine and Chlorhexidine Fail to Eradicate Staphylococcus aureus Biofilm from Infected Implant Materials.

Hydrogen peroxide, povidone-iodine, and chlorhexidine are antiseptics that are commonly added to irrigants to either prevent or treat infection. There are little clinical data available that demonstrate efficacy of adding antiseptics to irrigants in the treatment of periprosthetic joint infection after biofilm establishment. The objective of the study was to assess the bactericidal activity of the antiseptics on S. aureus planktonic and biofilm. For planktonic irrigation, S. aureus was exposed to different concentrations of antiseptics. S. aureus biofilm was developed by submerging a Kirschner wire into normalized bacteria and allowing it to grow for forty-eight hours. The Kirschner wire was then treated with irrigation solutions and plated for CFU analysis. Hydrogen peroxide, povidone-iodine, and chlorhexidine were bactericidal against planktonic bacteria with over a 3 log reduction (p < 0.0001). Unlike cefazolin, the antiseptics were not bactericidal (less than 3 log reduction) against biofilm bacteria but did have a statistical reduction in biofilm as compared to the initial time point (p < 0.0001). As compared to cefazolin treatment alone, the addition of hydrogen peroxide or povidone-iodine to cefazolin treatment only additionally reduced the biofilm burden by less than 1 log. The antiseptics demonstrated bactericidal properties with planktonic S. aureus; however, when used to irrigate S. aureus biofilms, these antiseptics were unable to decrease biofilm mass below a 3 log reduction, suggesting that S. aureus biofilm has a tolerance to antiseptics. This information should be considered when considering antibiotic tolerance in established S. aureus biofilm treatment.

Multiple micronutrient supplementation cost-benefit tool for informing maternal nutrition policy and investment decisions.

Antenatal multiple micronutrient supplementation (MMS) is an intervention that can help reach three of the six global nutrition targets, either directly or indirectly: a reduction in low birth weight, stunting, and anaemia in women of reproductive age. To support global guideline development and national decision-making on investments into maternal nutrition, Nutrition International developed a modelling tool called the MMS cost-benefit tool to help users understand whether antenatal MMS is better value for money than iron and folic acid supplementation (IFAS) during pregnancy. The MMS cost-benefit tool can generate estimates on the potential health impact, budget impact, economic value, cost-effectiveness and benefit-cost ratio of investing in MMS compared to IFAS in LMICs. In the 33 countries with data included in the tool, the MMS cost-benefit tool shows that transitioning is expected to generate substantial health benefits in terms of morbidity and mortality averted and can be very cost-effective in multiple scenarios for these countries. The cost per DALY averted averages at US$ 23.61 and benefit-cost ratio ranges from US$ 41-US$ 1304: $1.0, which suggest MMS is good value for money compared with IFAS. With its user-friendly design, open access availability, and online data-driven analytics, the MMS cost-benefit tool can be a powerful resource for governments and nutrition partners seeking timely and evidence-based analyses to inform policy-decision and investments towards the scale-up of MMS for pregnant women globally.

Overcoming biological barriers to improve treatment of a Staphylococcus aureus wound infection.

Chronic wounds frequently become infected with bacterial biofilms which respond poorly to antibiotic therapy. Aminoglycoside antibiotics are ineffective at treating deep-seated wound infections due to poor drug penetration, poor drug uptake into persister cells, and widespread antibiotic resistance. In this study, we combat the two major barriers to successful aminoglycoside treatment against a biofilm-infected wound: limited antibiotic uptake and limited biofilm penetration. To combat the limited antibiotic uptake, we employ palmitoleic acid, a host-produced monounsaturated fatty acid that perturbs the membrane of gram-positive pathogens and induces gentamicin uptake. This novel drug combination overcomes gentamicin tolerance and resistance in multiple gram-positive wound pathogens. To combat biofilm penetration, we examined the ability of sonobactericide, a non-invasive ultrasound-mediated-drug delivery technology to improve antibiotic efficacy using an in vivo biofilm model. This dual approach dramatically improved antibiotic efficacy against a methicillin-resistant Staphylococcus aureus (MRSA) wound infection in diabetic mice.

Antibiotic-induced accumulation of lipid II synergizes with antimicrobial fatty acids to eradicate bacterial populations.

Antibiotic tolerance and antibiotic resistance are the two major obstacles to the efficient and reliable treatment of bacterial infections. Identifying antibiotic adjuvants that sensitize resistant and tolerant bacteria to antibiotic killing may lead to the development of superior treatments with improved outcomes. Vancomycin, a lipid II inhibitor, is a frontline antibiotic for treating methicillin-resistant Staphylococcus aureus and other Gram-positive bacterial infections. However, vancomycin use has led to the increasing prevalence of bacterial strains with reduced susceptibility to vancomycin. Here, we show that unsaturated fatty acids act as potent vancomycin adjuvants to rapidly kill a range of Gram-positive bacteria, including vancomycin-tolerant and resistant populations. The synergistic bactericidal activity relies on the accumulation of membrane-bound cell wall intermediates that generate large fluid patches in the membrane leading to protein delocalization, aberrant septal formation, and loss of membrane integrity. Our findings provide a natural therapeutic option that enhances vancomycin activity against difficult-to-treat pathogens, and the underlying mechanism may be further exploited to develop antimicrobials that target recalcitrant infection.

Effectiveness of outpatient and community treatments for people with a diagnosis of 'personality disorder': systematic review and meta-analysis.

BACKGROUND: Quality of care and access to effective interventions have been widely criticised as limited for people diagnosed with 'personality disorder' or who have comparable needs (described in some recent papers as "Complex Emotional Needs" (CEN). It is important to identify effective interventions and the optimal context and mode of delivery for people with CEN. We aimed to investigate the effectiveness of psychosocial interventions delivered in community and outpatient settings in treating symptoms associated with 'personality disorder', and the moderating effects of treatment-related variables. METHODS: We systematically searched MEDLINE, EMBASE, PsycINFO, CINAHL, HMIC, ASSIA for articles published in English, from inception to November 23, 2020. We included randomized controlled trials examining interventions provided in community or outpatient settings for CEN. The primary outcome was 'personality disorder' symptoms, while secondary outcomes included anxiety symptoms, depressive symptoms, and global psychiatric symptoms. Random-effects meta-analysis was conducted for each outcome, and meta-regression analysis was performed to assess the moderating effects of treatment characteristics. The quality of the studies and the degree of publication bias was assessed. RESULTS: We included 54 trials (n = 3716 participants) in the meta-analysis. We found a large effect size (g = 0.78, 95% CI: 0.56 to 1.01, p < 0.0001) favoring interventions for 'borderline personality disorder' (BPD) symptoms over Treatment as Usual or Waitlist (TAU/WL), and the efficacy was maintained at follow-up (g = 1.01, 95% CI: 0.37 to 1.65, p = 0.002). Interventions effectively reduced anxiety symptoms (g = 0.58, 95% CI: 0.21 to 0.95, p = 0.002), depressive symptoms (g = 0.57, 95% CI: 0.32 to 0.83, p < 0.0001), and global psychiatric symptoms (g = 0.50, 95% CI: 0.35 to 0.66, p < 0.0001) compared to TAU/WL. The intervention types were equally effective in treating all symptom categories assessed. Treatment duration and treatment intensity did not moderate the effectiveness of the interventions for any outcome. CONCLUSIONS: People with a 'personality disorder' diagnosis benefited from psychological and psychosocial interventions delivered in community or outpatient settings, with all therapeutic approaches showing similar effectiveness. Mental health services should provide people with CEN with specialised treatments in accordance with the availability and the patients' preferences.

Consumption of Key Food Groups by Individuals Consuming Popular Diet Patterns: Mixed Effects of Replacing Foods High in Added Sugar, Sodium, Saturated Fat, and Refined Grains.

Adults in the United States are increasingly following 'popular' diet patterns that restrict food groups, macronutrients, or eating time. However, the intake of food groups associated with these diet patterns has not been well characterized. The objectives of this study were to (1) characterize the mean intake of food groups among consumers of popular diet patterns in the US, and (2) model the effect of targeted food substitutions on the intake of food groups. Data were acquired from the National Health and Nutrition Examination Survey, 2005-2018 (n = 34,411). A diet model was developed to assess the effects of replacing one serving each of foods highest in added sugar, sodium, saturated fat, and refined grains with healthy alternatives on the intake of key food groups for each diet pattern. Modeled replacement resulted in increased intake of fruit and whole grains and decreased intake of dairy for most diet patterns, while the effects on the intake of vegetables, protein foods, and oils were variable across diet patterns. The complexity of the natural eating environment, in which many people consume mixed dishes that include both healthy and less healthy ingredients, produces a challenge for health professionals when providing dietary counseling. Nevertheless, this substitution approach may help improve adherence to dietary guidelines, especially if used as a steppingstone for further dietary improvement.

Patients' and staff members' experiences of restrictive practices in acute mental health in-patient settings: systematic review and thematic synthesis.

BACKGROUND: Recent guidance has called for the reduction of restrictive practice use owing to growing concerns over the harmful physical and psychological effects for both patients and staff. Despite concerns and efforts, these measures continue to be used regularly to manage challenging behaviour in psychiatric in-patient settings. AIMS: To undertake a systematic review of patients' and staff members' experiences of restrictive practices in acute psychiatric in-patient settings. METHOD: A systematic review and thematic synthesis was conducted using data from 21 qualitative papers identified from a systematic search across three electronic databases (PsycInfo, Embase and MEDLINE) and citation searching. The protocol for the review was pre-registered on PROSPERO (CRD42020176859). The quality of included papers was examined using the Critical Appraisal Skills Programme (CASP). RESULTS: Four overarching themes emerged from the experiences of patients: the psychological effects, staff communication, loss of human rights and making changes. Likewise, the analysis of staff data produced four themes: the need for restrictive practices, the psychological impact, decision-making and making changes. Patient and staff experiences of restrictive practices were overwhelmingly negative, and their use carried harmful physical and psychological consequences. Lack of support following restraint events was a problem for both groups. CONCLUSIONS: Future programmes seeking to improve or reduce restrictive practices should consider the provision of staff training covering behaviour management and de-escalation techniques, offering psychological support to both patients and staff, the importance of effective staff-patient communication and the availability of alternatives.

Harm minimisation for self-harm: a cross-sectional survey of British clinicians' perspectives and practices.

OBJECTIVE: Harm minimisation for self-harm is an alternative to preventive strategies and focuses on maximising safety when self-harming. We explored the views of clinicians on harm minimisation for self-harm to describe reported use and acceptability in clinical practice. DESIGN: A cross-sectional study using an online survey consisting of fixed-choice and open-ended questions. SETTING: Primary and secondary care practices in England, Scotland and Wales. PARTICIPANTS: Snowball sampling of UK-based clinicians (n=90; 67% female) working with people who self-harm and who have or have not previously recommended harm minimisation methods to patients. RESULTS: Of the 90 clinicians sampled, 76 (84%) reported having recommended harm minimisation techniques to people in their care who self-harm. Commonly recommended techniques were snapping rubber bands on one's wrist and squeezing ice. Other techniques, such as teaching use of clean instruments when self-harming, were less likely to be recommended. Perceived client benefits included harm reduction and promotion of the therapeutic relationship. Perceived potential limitations of a harm minimisation approach for self-harm were (a) potential worsening of self-harm outcomes; (b) ethical reservations; (c) doubts about its effectiveness and appropriateness; and (d) lack of training and clear policies within the workplace. CONCLUSIONS: In our sample of UK-based clinicians in various settings, harm minimisation for self-harm was broadly recommended for clients who self-harm due to perceived client benefits. However, future policies on harm minimisation must address clinicians' perceived needs for training, well-defined guidelines, and clear evidence of effectiveness and safety to mitigate some clinician concerns about the potential for further harm.

Implementation of Delayed Cord Clamping in public health facilities: a case study from India.

BACKGROUND: Global and country specific recommendations on Delayed umbilical cord clamping (DCC) are available, though guidance on their implementation in program settings is lacking. In India, DCC (clamping not earlier than 1 min after birth) is a component in the package of services delivered as part of the India Newborn Action Plan (INAP) supported by Nutrition International (NI) in two states. The objective of this case study was to document the learnings from implementation of DCC in these two states and to understand the health system factors that affected its operationalization. METHODS: Mixed methods were followed. Using the World Health Organization (WHO) Health Systems building blocks as a framework, 20 Key-Informant Interviews were conducted to explore facilitators and barriers to routine implementation of DCC in public health settings. Existing quantitative program data and secondary data from labour-room registers from eight NI- supported districts were analysed to assess the prevalence of DCC implementation in public health systems settings. RESULTS: A demonstrated commitment from the government to implement DCC at all delivery points in NI supported districts was observed. Funds were sufficient, trainings were optimal, knowledge of the health workforce was adequate and a recording mechanism was in place. According to record reviews, DCC was more likely to happen in facilities that provide Basic Emergency Obstetric services and among normal deliveries. It was less likely to be followed in babies delivered by Caesarean section (OR 0.03; 95%CI 0.02,0.05), birthweight < 2000 g (OR 0.22; 95%CI 0.12,0.47), multiple pregnancies (OR 0.17, 95%CI 0.05,0.63), birth asphyxia requiring resuscitation (0.37; 95%CI 0.26,0.52), and those delivered during day shift (OR 0.59, 95%CI 0.40, 0.83). CONCLUSIONS: Wide coverage of DCC in public health settings in the two states was observed. Good governance, adequate funding, commitment of health workforce has likely contributed to its success in these contexts. These are critical elements to guide DCC implementation in India and for consideration in other settings.

Increased viral load in a hospitalized patient on treatment with crushed bictegravir/emtricitabine/tenofovir alafenamide: A case report and review of the literature.

PURPOSE: To describe a case of increased viral load in a patient with HIV-1 infection receiving treatment with crushed bictegravir/emtricitabine/tenofovir alafenamide (B/FTC/TAF). SUMMARY: A 43-year-old man, newly diagnosed with HIV, was hospitalized due to failure to thrive, neurological changes, and hypotension. Before treatment, the HIV viral load (VL) was 769,704 copies/mL and the CD4+ T-cell count was 36 cells/µL. On hospital day (HD) 8, B/FTC/TAF by mouth daily was initiated. During the hospitalization, the patient's course was complicated by opportunistic infections, bilateral pneumothorax, seizure activity, and acute respiratory distress, requiring multiple intubations and extended time in the intensive care unit. A repeat VL measurement on HD 28 was 5,887 copies/mL after the patient had received 14 of 20 scheduled B/FTC/TAF doses. Because of a failed swallow study and continued nutritional deficits, a percutaneous endoscopic gastrostomy (PEG) tube was placed on HD 38 and continuous tube feeds via the PEG tube were initiated. Subsequently, the B/FTC/TAF order was modified to be crushed, mixed in 30 mL water, and administered daily via the PEG tube. A repeat VL measurement on HD 65 showed an increase to 8,047 copies/mL, despite receipt of 37 consecutive doses of B/FTC/TAF. B/FTC/TAF was discontinued and dolutegravir 50 mg twice daily, darunavir 800 mg plus ritonavir 100 mg (DRV/r), and tenofovir disoproxil fumarate/FTC 300 mg/200 mg were started due to virological increase, need for a viable option compatible with PEG tube delivery, and potential for integrase inhibitor resistance. At the time of regimen change (HD 67), a resistance panel showed minor mutations, E157Q and V118I. The regimen was streamlined with discontinuation of DRV/r on HD 92. The patient was discharged on HD 161. The PEG tube was removed 2 months after discharge, oral B/FTC/TAF was reinitiated, and the patient was virologically suppressed at 1 year after discharge. CONCLUSION: Controlled studies are needed to verify acceptable pharmacokinetic and pharmacodynamic metrics for crushed B/FTC/TAF given via tube, with and without tube feeds, before use in this manner.

The Use of Acute Immunosuppressive Therapy to Improve Antibiotic Efficacy against Intracellular Staphylococcus aureus.

Interactions between Staphylococcus aureus and the host immune system can have significant impacts on antibiotic efficacy, suggesting that targeting and modulating the immune response to S. aureus infection may improve antibiotic efficacy and improve infection outcome. As we've previously shown, high levels of reactive oxygen species (ROS), associated with an M1-like proinflammatory macrophage response, potently induce antibiotic tolerance in S. aureus. Although the proinflammatory immune response is critical for initial control of pathogen burden, recent studies demonstrate that modulation of the macrophage response to an anti-inflammatory, or M2-like, response facilitates resolution of established S. aureus skin and soft tissue infections, arthritis, and bacteremia. Here, we evaluated the impact of host-directed immunosuppressive chemotherapeutics and anti-inflammatory agents on antibiotic efficacy against S. aureus. IMPORTANCE Staphylococcus aureus is the leading cause of hospital-acquired infections in the United States with high rates of antibiotic treatment failure. Macrophages represent an important intracellular niche in experimental models of S. aureus bacteremia. Although a proinflammatory macrophage response is critical for controlling infection, previous studies have identified an antagonistic relationship between antibiotic treatment and the proinflammatory macrophage response. Reactive oxygen species, produced by macrophages during respiratory burst, coerce S. aureus into an antibiotic tolerant state, leading to poor treatment outcome. Here, we aimed to determine the potential of host-directed immunomodulators that reduce the production of reactive oxygen species to improve antibiotic efficacy against intracellular S. aureus.