Bacteriophages and bacterial plant diseases

Losses in crop yields due to disease need to be reduced in order to meet increasing global food demands associated with growth in the human population. There is a well-recognized need to develop new environmentally friendly control strategies to combat bacterial crop disease. Current control measures involving the use of traditional chemicals or antibiotics are losing their efficacy due to the natural development of bacterial resistance to these agents. In addition, there is an increasing awareness that their use is environmentally unfriendly. Bacteriophages, the viruses of bacteria, have received increased research interest in recent years as a realistic environmentally friendly means of controlling bacterial diseases. Their use presents a viable control measure for a number of destructive bacterial crop diseases, with some phage-based products already becoming available on the market. Phage biocontrol possesses advantages over chemical controls in that tailor-made phage cocktails can be adapted to target specific disease-causing bacteria. Unlike chemical control measures, phage mixtures can be easily adapted for bacterial resistance which may develop over time. In this review, we will examine the progress and challenges for phage-based disease biocontrol in food crops

Bacteriophage-Derived Peptidase CHAP

New antibacterial agents are urgently needed for the elimination of biofilm-forming bacteria that are highly resistant to traditional antimicrobial agents. Proliferation of such bacteria can lead to significant economic losses in the agri-food sector. This study demonstrates the potential of the bacteriophage-derived peptidase, CHAPK, as a biocidal agent for the rapid disruption of biofilm-forming staphylococci, commonly associated with bovine mastitis. Purified CHAPK applied to biofilms of Staphylococcus aureus DPC5246 completely eliminated the staphylococcal biofilms within 4 h. In addition, CHAPK was able to prevent biofilm formation by this strain. The CHAPK lysin also reduced S. aureus in a skin decolonization model. Our data demonstrates the potential of CHAPK as a biocidal agent for prevention and treatment of biofilm-associated staphylococcal infections or as a decontaminating agent in the food and healthcare sectors

Genome sequence of jumbo phage vB_AbaM_ME3 of Acinetobacter baumanni

Bacteriophage (phage) vB_AbaM_ME3 was previously isolated from wastewater effluent using the propagating host Acinetobacter baumannii DSM 30007. The full genome was sequenced, revealing it to be the largest Acinetobacter bacteriophage sequenced to date with a size of 234,900 bp and containing 326 open reading frames (ORFs)

Experience of hospital-initiated medication changes in older people with multimorbidity: a multicentre mixed-methods study embedded in the OPtimising thERapy to prevent Avoidable hospital admissions in Multimorbid older people (OPERAM) trial.

BACKGROUND A patient-centred approach to medicines optimisation is considered essential. The OPtimising thERapy to prevent Avoidable hospital admissions in Multimorbid older people (OPERAM) trial evaluated the effectiveness of medication review with shared decision-making (SDM) in older people with multimorbidity. Beyond evaluating the clinical effectiveness, exploring the patient experience facilitates a better understanding of contextual factors and mechanisms affecting medication review effectiveness. OBJECTIVE To explore experiences of hospital-initiated medication changes in older people with multimorbidity. METHODS We conducted a multicentre mixed-methods study, embedded in the OPERAM trial, combining semi-structured interviews and the Beliefs about Medicines Questionnaire (BMQ) with a purposive sample of 48 patients (70-94 years) from four European countries. Interviews were analysed using the Framework approach. Trial implementation data on SDM were collected and the 9-item SDM questionnaire was conducted with 17 clinicians. RESULTS Patients generally displayed positive attitudes towards medication review, yet emphasised the importance of long-term, trusting relationships such as with their general practitioners for medication review. Many patients reported a lack of information and communication about medication changes and predominantly experienced paternalistic decision-making. Patients' beliefs that 'doctors know best', 'blind trust', having limited opportunities for questions, use of jargon terms by clinicians, 'feeling too ill', dismissive clinicians, etc highlight the powerlessness some patients felt during hospitalisation, all representing barriers to SDM. Conversely, involvement of companions, health literacy, empathetic and trusting patient-doctor relationships, facilitated SDM. Paradoxical to patients' experiential accounts, clinicians reported high levels of SDM. The BMQ showed that most patients had high necessity and low concern beliefs about medicines. Beliefs about medicines, experiencing benefits or harms from medication changes, illness perception, trust and balancing advice between different healthcare professionals all affected acceptance of medication changes. CONCLUSION To meet patients' needs, future medicines optimisation interventions should enhance information exchange, better prepare patients and clinicians for partnership in care and foster collaborative medication reviews across care settings

HOSPITAL Score and LACE Index to Predict Mortality in Multimorbid Older Patients.

BACKGROUND Estimating life expectancy of older adults informs whether to pursue future investigation and therapy. Several models to predict mortality have been developed but often require data not immediately available during routine clinical care. The HOSPITAL score and the LACE index were previously validated to predict 30-day readmissions but may also help to assess mortality risk. We assessed their performance to predict 1-year and 30-day mortality in hospitalized older multimorbid patients with polypharmacy. METHODS We calculated the HOSPITAL score and LACE index in patients from the OPERAM (OPtimising thERapy to prevent Avoidable hospital admissions in the Multimorbid elderly) trial (patients aged ≥ 70 years with multimorbidity and polypharmacy, admitted to hospital across four European countries in 2016-2018). Our primary and secondary outcomes were 1-year and 30-day mortality. We assessed the overall accuracy (scaled Brier score, the lower the better), calibration (predicted/observed proportions), and discrimination (C-statistic) of the models. RESULTS Within 1 year, 375/1879 (20.0%) patients had died, including 94 deaths within 30 days. The overall accuracy was good and similar for both models (scaled Brier score 0.01-0.08). The C-statistics were identical for both models (0.69 for 1-year mortality, p = 0.81; 0.66 for 30-day mortality, p = 0.94). Calibration showed well-matching predicted/observed proportions. CONCLUSION The HOSPITAL score and LACE index showed similar performance to predict 1-year and 30-day mortality in older multimorbid patients with polypharmacy. Their overall accuracy was good, their discrimination low to moderate, and the calibration good. These simple tools may help predict older multimorbid patients' mortality after hospitalization, which may inform post-hospitalization intensity of care

Drug-related readmissions in older hospitalized adults: External validation and updating of OPERAM DRA prediction tool.

BACKGROUND Drug-related readmissions (DRAs) are defined as rehospitalizations with an adverse drug event as their main or significant contributory cause. DRAs represent a major adverse health burden for older patients. A prediction model which identified older hospitalized patients at high risk of a DRA <1 year was previously developed using the OPERAM trial cohort, a European cluster randomized controlled trial including older hospitalized patients with multimorbidity and polypharmacy. This study has performed external validation and updated the prediction model consequently. METHODS The MedBridge trial cohort (a multicenter cluster randomized crossover trial performed in Sweden) was used as a validation cohort. It consisted of 2516 hospitalized patients aged ≥65 years. Model performance was assessed by: (1) discriminative power, assessed by the C-statistic with a 95% confidence interval (CI); (2) calibration, assessed by visual examination of the calibration plot and use of the Hosmer-Lemeshow goodness-of-fit test; and (3) overall accuracy, assessed by the scaled Brier score. Several updating methods were carried out to improve model performance. RESULTS In total, 2516 older patients were included in the validation cohort, of whom 582 (23.1%) experienced a DRA <1 year. In the validation cohort, the original model showed a good overall accuracy (scaled Brier score 0.03), but discrimination was moderate (C-statistic 0.62 [95% CI 0.59-0.64]), and calibration showed underestimation of risks. In the final updated model, the predictor "cirrhosis with portal hypertension" was removed and "polypharmacy" was added. This improved the model's discriminative capability to a C-statistic of 0.64 (95% CI 0.59-0.70) and enhanced calibration plots. Overall accuracy remained good. CONCLUSIONS The updated OPERAM DRA prediction model may be a useful tool in clinical practice to estimate the risk of DRAs in older hospitalized patients subsequent to discharge. Our efforts lay the groundwork for the future development of models with even better performance

Benzodiazepine Receptor Agonists Use and Cessation Among Multimorbid Older Adults with Polypharmacy: Secondary Analysis from the OPERAM Trial

BACKGROUND Benzodiazepine receptor agonists (BZRAs) are commonly prescribed in older adults despite an unfavorable risk-benefit ratio. Hospitalizations may provide a unique opportunity to initiate BZRA cessation, yet little is known about cessation during and after hospitalization. We aimed to measure the prevalence of BZRA use before hospitalization and the rate of cessation 6 months later, and to identify factors associated with these outcomes. METHODS We conducted a secondary analysis of a cluster randomized controlled trial (OPtimising thERapy to prevent Avoidable hospital admissions in the Multimorbid elderly [OPERAM]), comparing usual care and in-hospital pharmacotherapy optimization in adults aged 70 years or over with multimorbidity and polypharmacy in four European countries. BZRA cessation was defined as taking one or more BZRA before hospitalization and not taking any BZRA at the 6-month follow-up. Multivariable logistic regression was performed to identify factors associated with BZRA use before hospitalization and with cessation at 6 months. RESULTS Among 1601 participants with complete 6-month follow-up data, 378 (23.6%) were BZRA users before hospitalization. Female sex (odds ratio [OR] 1.52 [95% confidence interval 1.18-1.96]), a higher reported level of depression/anxiety (OR up to 2.45 [1.54-3.89]), a higher number of daily drugs (OR 1.08 [1.05-1.12]), use of an antidepressant (OR 1.74 [1.31-2.31]) or an antiepileptic (OR 1.46 [1.02-2.07]), and trial site were associated with BZRA use. Diabetes mellitus (OR 0.60 [0.44-0.80]) was associated with a lower probability of BZRA use. BZRA cessation occurred in 86 BZRA users (22.8%). Antidepressant use (OR 1.74 [1.06-2.86]) and a history of falling in the previous 12 months (OR 1.75 [1.10-2.78]) were associated with higher BZRA cessation, and chronic obstructive pulmonary disease (COPD) (OR 0.45 [0.20-0.91]) with lower BZRA cessation. CONCLUSION BZRA prevalence was high among included multimorbid older adults, and BZRA cessation occurred in almost a quarter of them within 6 months after hospitalization. Targeted BZRA deprescribing programs could further enhance cessation. Specific attention is needed for females, central nervous system-acting co-medication, and COPD co-morbidity. REGISTRATION ClinicalTrials.gov identifier: NCT02986425. December 8, 2016

Benzodiazepine Receptor Agonists Use and Cessation Among Multimorbid Older Adults with Polypharmacy: Secondary Analysis from the OPERAM Trial.

BACKGROUND Benzodiazepine receptor agonists (BZRAs) are commonly prescribed in older adults despite an unfavorable risk-benefit ratio. Hospitalizations may provide a unique opportunity to initiate BZRA cessation, yet little is known about cessation during and after hospitalization. We aimed to measure the prevalence of BZRA use before hospitalization and the rate of cessation 6 months later, and to identify factors associated with these outcomes. METHODS We conducted a secondary analysis of a cluster randomized controlled trial (OPtimising thERapy to prevent Avoidable hospital admissions in the Multimorbid elderly [OPERAM]), comparing usual care and in-hospital pharmacotherapy optimization in adults aged 70 years or over with multimorbidity and polypharmacy in four European countries. BZRA cessation was defined as taking one or more BZRA before hospitalization and not taking any BZRA at the 6-month follow-up. Multivariable logistic regression was performed to identify factors associated with BZRA use before hospitalization and with cessation at 6 months. RESULTS Among 1601 participants with complete 6-month follow-up data, 378 (23.6%) were BZRA users before hospitalization. Female sex (odds ratio [OR] 1.52 [95% confidence interval 1.18-1.96]), a higher reported level of depression/anxiety (OR up to 2.45 [1.54-3.89]), a higher number of daily drugs (OR 1.08 [1.05-1.12]), use of an antidepressant (OR 1.74 [1.31-2.31]) or an antiepileptic (OR 1.46 [1.02-2.07]), and trial site were associated with BZRA use. Diabetes mellitus (OR 0.60 [0.44-0.80]) was associated with a lower probability of BZRA use. BZRA cessation occurred in 86 BZRA users (22.8%). Antidepressant use (OR 1.74 [1.06-2.86]) and a history of falling in the previous 12 months (OR 1.75 [1.10-2.78]) were associated with higher BZRA cessation, and chronic obstructive pulmonary disease (COPD) (OR 0.45 [0.20-0.91]) with lower BZRA cessation. CONCLUSION BZRA prevalence was high among included multimorbid older adults, and BZRA cessation occurred in almost a quarter of them within 6 months after hospitalization. Targeted BZRA deprescribing programs could further enhance cessation. Specific attention is needed for females, central nervous system-acting co-medication, and COPD co-morbidity. REGISTRATION ClinicalTrials.gov identifier: NCT02986425. December 8, 2016

Impact of therapeutic hypothermia on infantile spasms: an observational cohort study

Aim: To establish the incidence of infantile spasms in children in the southern region of the Republic of Ireland and to compare the incidence of infantile spasms before and after the introduction of therapeutic hypothermia in infants with hypoxic‐ischemic encephalopathy (HIE). Method: Children born between 2003 and 2015 and diagnosed with infantile spasms (epileptic spasms with or without hypsarrhythmia) in the first 2 years of life were identified through audits of electroencephalography reports and paediatric neurology patient lists. Data on live births were obtained from the regional hospital statistics databases. Medical charts of infantile spasm cases were reviewed for demographic information, diagnostic workup results, treatment response, disease course, and developmental outcome. Results: Forty‐two infants with infantile spasms were identified. The cumulative incidence of infantile spasms up to the age of 2 years was 4.01 per 10 000 live births. Difference due to sex was minimal (22 males, 20 females) and most infants were delivered at or near term with gestational ages ranging between 30.0 and 41.8 weeks (median [interquartile range] 39.6wks [38.1–40.0wks]). The aetiology for infantile spasms was identified in almost two‐thirds of cases, with HIE being the single most common cause (n=7). Other causes included chromosomal and monogenetic abnormalities (n=8). Infantile spasms occurred in moderate and severe grades of HIE, with a significantly higher incidence in those with severe HIE (p=0.029). Infants with severe HIE who did not receive therapeutic hypothermia were six times more likely to develop infantile spasms compared to those who did, but the difference was not statistically significant (4 out of 16 vs 1 out of 24, p=0.138). Interpretation: This study provides detailed information about infantile spasms before and after the introduction of therapeutic hypothermia. HIE severity is a risk factor for the development of infantile spasms. The introduction of therapeutic hypothermia may have had an impact, but the effect was hard to ascertain in this cohort due to the small number of infants

Programming bugs: microbiota and the developmental origins of brain health and disease

It has been nearly 30 years since Dr. David Barker first highlighted the importance of prenatal factors in contributing to the developmental origins of adult disease. This concept was later broadened to include postnatal events. It is clear that the interaction between genetic predisposition and early life environmental exposures is key in this regard. However, recent research has also identified another important factor in the microbiota—the trillions of microorganisms that inhabit key body niches, including the vagina and gastrointestinal tract. Because the composition of these maternal microbiome sites has been linked to maternal metabolism and is also vertically transmitted to offspring, changes in the maternal microbiota are poised to significantly affect the newborn. In fact, several lines of evidence show that the gut microbiota interacts with diet, drugs, and stress both prenatally and postnatally and that these exogenous factors could also affect the dynamic changes in the microbiota composition occurring during pregnancy. Animal models have shown great utility in illuminating how these disruptions result in behavioral and brain morphological phenotypes reminiscent of psychiatric disorders (anxiety, depression, schizophrenia, and autism spectrum disorders). Increasing evidence points to critical interactions among the microbiota, host genetics, and both the prenatal and postnatal environments to temporally program susceptibility to psychiatric disorders later in life. Sex-specific phenotypes may be programmed through the influence of the microbiota on the hypothalamic-pituitary-adrenal axis and neuroimmune system