Exploring the synthetic potential of a marine transaminase including discrimination at a remote stereocentre.

The marine transaminase, P-ω-TA, can be employed for the transamination from 1-aminotetralins and 1-aminoindanes with differentiation of stereochemistry at both the site of reaction and at a remote stereocentre resulting in formation of ketone products with up to 93% ee. While 4-substituents are tolerated on the tetralin core, the presence of 3- or 8-substituents is not tolerated by the transaminase. In general P-ω-TA shows capacity for remote diastereoselectivity, although both the stereoselectivity and efficiency are dependent on the specific substrate structure. Optimum efficiency and selectivity are seen with 4-haloaryl-1-aminotetralins and 3-haloaryl-1-aminoindanes, which may be associated with the marine origin of this enzyme.

Palliative care interventions in advanced dementia.

BACKGROUND: Dementia is a chronic, progressive and ultimately fatal neurodegenerative disease. Advanced dementia is characterised by profound cognitive impairment, inability to communicate verbally and complete functional dependence. Usual care of people with advanced dementia is not underpinned universally by a palliative approach. Palliative care has focused traditionally on care of people with cancer, but for more than a decade, there have been calls worldwide to extend palliative care services to include all people with life-limiting illnesses in need of specialist care, including people with dementia. This review is an updated version of a review first published in 2016. OBJECTIVES: To assess the effect of palliative care interventions in advanced dementia. SEARCH METHODS: We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group's Specialised Register on 7 October 2020. ALOIS contains records of clinical trials identified from monthly searches of several major healthcare databases, trial registries and grey literature sources. We ran additional searches across MEDLINE (OvidSP), Embase (OvidSP), four other databases and two trial registries on 7 October 2020 to ensure that the searches were as comprehensive and as up-to-date as possible. SELECTION CRITERIA: We searched for randomised (RCTs) and non-randomised controlled trials (nRCTs), controlled before-and-after studies and interrupted time series studies evaluating the impact of palliative care interventions for adults with advanced dementia of any type. Participants could be people with advanced dementia, their family members, clinicians or paid care staff. We included clinical interventions and non-clinical interventions. Comparators were usual care or another palliative care intervention. We did not exclude studies based on outcomes measured. DATA COLLECTION AND ANALYSIS: At least two review authors (SW, EM, PC) independently assessed all potential studies identified in the search against the review inclusion criteria. Two authors independently extracted data from eligible studies. Where appropriate, we estimated pooled treatment effects in a fixed-effect meta-analysis. We assessed the risk of bias of included studies using the Cochrane Risk of Bias tool and the overall certainty of the evidence for each outcome using GRADE. MAIN RESULTS: Nine studies (2122 participants) met the review inclusion criteria. Two studies were individually-randomised RCTs, six were cluster-randomised RCTs and one was a controlled before-and-after study. We conducted two separate comparisons: organisation and delivery of care interventions versus usual care (six studies, 1162 participants) and advance care planning interventions versus usual care (three studies, 960 participants). Two studies were carried out in acute hospitals and seven in nursing homes or long-term care facilities. For both comparisons, we found the included studies to be sufficiently similar to conduct meta-analyses. Changes to the organisation and delivery of care for people with advanced dementia may increase comfort in dying (MD 1.49, 95% CI 0.34 to 2.64; 5 studies, 335 participants; very low certainty evidence). However, the evidence is very uncertain and unlikely to be clinically significant. These changes may also increase the likelihood of having a palliative care plan in place (RR 5.84, 95% CI 1.37 to 25.02; 1 study, 99 participants; I2 = 0%; very low certainty evidence), but again the evidence is very uncertain. Such interventions probably have little effect on the use of non-palliative interventions (RR 1.11, 95% CI 0.71 to 1.72; 2 studies, 292 participants; I2 = 0%; moderate certainty evidence). They may also have little or no effect on documentation of advance directives (RR 1.46, 95% CI 0.50 to 4.25; 2 studies, 112 participants; I2 = 52%; very low certainty evidence), or whether discussions take place about advance care planning (RR 1.08, 95% CI 1.00 to 1.18; 1 study, 193 participants; I2 = 0%; very low certainty evidence) and goals of care (RR 2.36, 95% CI 1.00 to 5.54; 1 study, 13 participants; I2 = 0%; low certainty evidence). No included studies assessed adverse effects. Advance care planning interventions for people with advanced dementia probably increase the documentation of advance directives (RR 1.23, 95% CI 1.07 to 1.41; 2 studies, 384; moderate certainty evidence) and the number of discussions about goals of care (RR 1.33, 95% CI 1.11 to 1.59; 2 studies, 384 participants; moderate certainty evidence). They may also slightly increase concordance with goals of care (RR 1.39, 95% CI 1.08 to 1.79; 1 study, 63 participants; low certainty evidence). On the other hand, they may have little or no effect on perceived symptom management (MD -1.80, 95% CI -6.49 to 2.89; 1 study, 67 participants; very low certainty evidence) or whether advance care planning discussions occur (RR 1.04, 95% CI 0.87 to 1.24; 1 study, 67 participants; low certainty evidence). AUTHORS' CONCLUSIONS: The evidence on palliative care interventions in advanced dementia is limited in quantity and certainty. When compared to usual care, changes to the organisation and delivery of care for people with advanced dementia may lead to improvements in comfort in dying, but the evidence for this was of very low certainty. Advance care planning interventions, compared to usual care, probably increase the documentation of advance directives and the occurrence of discussions about goals of care, and may also increase concordance with goals of care. We did not detect other effects. The uncertainty in the evidence across all outcomes in both comparisons is mainly driven by imprecision of effect estimates and risk of bias in the included studies.

Alcohol Use Disorder and Comorbid Depression: A Randomized Controlled Trial Investigating the Effectiveness of Supportive Text Messages in Aiding Recovery.

AIM: The aim of this randomized controlled trial was to examine the impact of daily supportive text messages over a 6-month treatment period on mood and alcohol consumption in individuals with a dual diagnosis of alcohol use disorder (AUD) and depression following completion of an inpatient treatment programme. METHOD: Ninety-five adult participants with AUD and comorbid depression were recruited into this randomized control trial, which took place after completing a 30-day rehabilitation programme. The intervention group (n = 47) received twice-daily supportive text messages over 6-months while control participants (n = 48) had treatment as usual for a 6-month period, with an added 6-month post-treatment follow-up for both groups. Drinking history in the previous 90 days as well as symptoms of depression, anxiety and stress were measured at baseline, 3- and 6-month treatment points and 6-month post treatment follow up. RESULTS: Depression scores (P = 0.02) and perceived stress scores (P < 0.01) were significantly reduced at 3-month treatment point in the intervention group relative to control participants with small to medium effect. The intervention group also showed a significantly greater reduction in units per drinking day from baseline to 6-month treatment point compared to the control group with a medium effect size (P = 0.03). There were no differences in drinking or mood measures at 6-month post treatment follow-up. CONCLUSIONS: Supportive text messages provide an early initial benefit in decreasing symptoms of depression and stress, with a further positive impact on alcohol consumption following a longer treatment period. Benefits did not persist six months after the intervention ended.

Patient reported health status and all-cause mortality in patients with coronary heart disease.

Purpose: Patients with coronary heart disease (CHD) experience reduced quality of life which may be associated with mortality in the longer term. This study explores whether patient-rated physical and mental health status was associated with mortality at 6-year follow-up among patients with CHD attending primary care in Ireland and Northern Ireland. Methods: This study is a secondary data analysis of patients with CHD recruited to a cluster randomized controlled trial from 2004 to 2010. Data collected included patient-rated physical component summary (PCS) and mental component summary (MCS) scores of health status (from the 12-Item Short-Form Health Survey (SF-12)), demographics and clinical parameters at baseline, and all-cause mortality at 6-year follow-up. Multivariate regression was conducted using generalized estimating equations (GEE) with a log-link function. Results are presented as odds ratios (ORs) and 95% confidence intervals (CIs). Results: The study consisted of 762 individuals with mean age 67.6 years [standard deviation (SD): 9.8], and was 29% female. Mean baseline SF-12 mental (MCS) and physical (PCS) component scores were 50.0 (SD: 10.8) and 39.6 (SD: 11.2), respectively. At 6-year follow-up, the adjusted OR for the baseline MCS for mortality was 0.97 (95% CI: 0.95-0.99) and for the PCS 0.97 (95% CI: 0.95-0.99). For every five-point increase in MCS and PCS scores, there was a 14% reduction in the likelihood of all-cause mortality. Conclusions: Overall, the magnitude of effect for both mental health status and physical health status was similar; higher scores were significantly associated with a lower risk of mortality at 6-year follow-up.

Optimizing storage temperature of liquid bovine semen diluted in INRA96.

Temperature regulation of liquid bovine semen can be difficult in field situations. Two experiments were carried out to assess the effect of storage temperature on in vitro sperm characteristics and 60-d nonreturn rate (NRR) following artificial insemination (AI) of liquid bovine semen. In experiment 1, the effect of storage of liquid bovine semen in INRA96 diluent (IMV Technologies, L'Aigle, France) at 1 of 5 storage temperatures (5, 15, or 28°C, and fluctuating between 5 and 15°C or 5 and 28°C) on total and progressive motility and kinematic parameters was assessed objectively via computer-assisted sperm analyzer on d 0, 1, 2, 3, and 4 after collection. Fluctuating temperatures were designed to mimic day- to nighttime variation. In experiment 2, we assessed the field fertility of liquid semen stored at a constant 5 or 15°C or in an unregulated manner and compared with that of frozen-thawed semen (total of n = 106,738 inseminations). In experiment 1, we detected a linear decrease in motility with increased duration of storage. Semen stored at a constant 15°C or fluctuating between 5 and 15°C had greater total motility than semen held at 5 or 28°C or fluctuating between 5 and 28°C; however, semen stored at 15°C and fluctuating between 5 and 15°C did not differ from each other. Semen held at a constant 5 or 15°C or fluctuating between 5 and 15°C, although not differing from each other, had higher progressive motility scores than that held at 28°C or fluctuating between 5 and 28°C. Semen stored at a constant 28°C exhibited poor motility and velocity values but had high progressive motion values compared with that all other storage temperatures; however, the other storage temperatures did not differ from each other in relation to motility kinematics. In experiment 2, semen stored at a constant 5°C resulted in a lower 60-d NRR (62.5%) than storage at constant 15°C or unregulated temperature or frozen-thawed semen (73.6, 74.6, and 74.4%, respectively. In conclusion, sperm stored in IRNA96 are quite tolerant in terms of storage temperature, retaining acceptable motility between 5 and 15°C. Storing semen at a constant 15°C resulted in greater in vitro sperm motility and higher NRR rates than storage at 5°C and did not differ in NRR from frozen-thawed semen or semen stored at an unregulated temperature; however, lower storage temperatures were shown to be more detrimental to sperm in vivo than unregulated storage conditions.

A comparison of semen diluents on the in vitro and in vivo fertility of liquid bull semen.

The aim of this study was to assess the effect of semen diluent on calving rate (CR) following artificial insemination with liquid bull semen stored for up to 3 d postcollection. In experiment 1, the effect of storing liquid semen maintained at a constant ambient temperature in 1 of 7 different diluents [Caprogen (homemade), OptiXcell, BioXcell, BullXcell, INRA96, NutriXcell, or AndroMed (all commercially available)] on total and progressive motility was assessed on d 0, 1, 2, and 3 postcollection. In experiment 2, the field fertility of liquid semen diluted in Caprogen, BioXcell, or INRA96 and inseminated on d 1, 2, or 3 postcollection was assessed in comparison to frozen-thawed semen (total of n = 19,126 inseminations). In experiment 3, the effect of storage temperature fluctuations (4 and 18°C) on total and progressive motility following dilution in Caprogen, BioXcell, and INRA96 was assessed on d 0, 1, 2, and 3 postcollection. In experiment 1, semen stored in Caprogen, BioXcell, and INRA96 resulted in the highest total and progressive motility on d 1, 2, and 3 of storage compared with OptiXcell, BullXcell, NutriXcell, and AndroMed. In experiment 2, an effect of diluent on CR was found as semen diluted in BioXcell had a lower CR on d 1, 2, and 3 of storage (46.3, 35.4, and 34.0%, respectively) in comparison with Caprogen (55.8, 52.0, and 51.9%, respectively), INRA96 (55.0, 55.1, and 52.2%, respectively), and frozen-thawed semen (59.7%). Effects were found of parity, cow fertility sub-index, as well as the number of days in milk on CR. In experiment 3, when the storage temperature of diluted semen fluctuated between 4 and 18°C, to mimic what occurs in the field (nighttime vs. daytime), BioXcell had the lowest total and progressive motility in comparison to Caprogen and INRA96. In conclusion, diluent significantly affected sperm motility when stored for up to 3 d. Semen diluted in INRA96 resulted in a similar CR to semen diluted in Caprogen and to frozen-thawed semen, whereas that diluted in BioXcell resulted in a decreased CR. Consistent with this finding, semen diluted in BioXcell was less tolerant of temperature fluctuations than that stored in Caprogen or INRA96. Given that it can be used directly off the shelf, INRA96 may be a suitable alternative to Caprogen for the storage of liquid bull semen.

Palliative care interventions in advanced dementia.

BACKGROUND: Dementia is a chronic, progressive and ultimately fatal neurodegenerative disease. Advanced dementia is characterised by profound cognitive impairment, inability to communicate verbally and complete functional dependence. Usual care of people with advanced dementia is not underpinned universally by a palliative approach. Palliative care has focused traditionally on care of people with cancer but for more than a decade, there have been increased calls worldwide to extend palliative care services to include all people with life-limiting illnesses in need of specialist care, including people with dementia. OBJECTIVES: To assess the effect of palliative care interventions in advanced dementia and to report on the range of outcome measures used. SEARCH METHODS: We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group's Specialized Register on 4 February 2016. ALOIS contains records of clinical trials identified from monthly searches of several major healthcare databases, trial registries and grey literature sources. We ran additional searches across MEDLINE (OvidSP), Embase (OvidSP), PsycINFO (OvidSP), CINAHL (EBSCOhost), LILACS (BIREME), Web of Science Core Collection (ISI Web of Science), ClinicalTrials.gov and the World Health Organization ICTRP trial portal to ensure that the searches were as comprehensive and as up-to-date as possible. SELECTION CRITERIA: We searched for randomised (RCT) and non-randomised controlled trials (nRCT), controlled before-and-after studies (CBA) and interrupted time series studies evaluating the impact of palliative care interventions for adults with dementia of any type, staged as advanced dementia by a recognised and validated tool. Participants could be people with advanced dementia, their family members, clinicians or paid care staff. We included clinical interventions and non-clinical interventions. Comparators were usual care or another palliative care intervention. We did not exclude studies on the basis of outcomes measured and recorded all outcomes measured in included studies. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed for inclusion all the potential studies we identified as a result of the search strategy. We resolved any disagreement through discussion or, when required, consulted with the rest of the review team. We independently extracted data and conducted assessment of methodological quality, using standard Cochrane methods. MAIN RESULTS: We identified two studies of palliative care interventions for people with advanced dementia. We did not pool data due to the heterogeneity between the two trials in terms of the interventions and the settings. The two studies measured 31 different outcomes, yet they did not measure the same outcome. There are six ongoing studies that we expect to include in future versions of this review.Both studies were at high risk of bias, in part because blinding was not possible. This and small sample sizes meant that the overall certainty of all the evidence was very low.One individually randomised RCT (99 participants) evaluated the effect of a palliative care team for people with advanced dementia hospitalised for an acute illness. While this trial reported that a palliative care plan was more likely to be developed for participants in the intervention group (risk ratio (RR) 5.84, 95% confidence interval (CI) 1.37 to 25.02), the plan was only adopted for two participants, both in the intervention group, while in hospital. The palliative care plan was more likely to be available on discharge in the intervention group (RR 4.50, 95% CI 1.03 to 19.75). We found no evidence that the intervention affected mortality in hospital (RR 1.06, 95% CI 0.53 to 2.13), decisions to forgo cardiopulmonary resuscitation in hospital or the clinical care provided during hospital admission, but for the latter, event rates were low and the results were associated with a lot of uncertainty.One cluster RCT (256 participants, each enrolled with a family carer) evaluated the effect of a decision aid on end-of-life feeding options on surrogate decision-makers of nursing home residents with advanced dementia. Data for 90 participants (35% of the original study) met the definition of advanced dementia for this review and were re-analysed for the purposes of the review. In this subset, intervention surrogates had lower scores for decisional conflict measured on the Decisional Conflict Scale (mean difference -0.30, 95% CI -0.61 to 0.01, reduction of 0.3 to 0.4 units considered meaningful) and were more likely than participants in the control group to discuss feeding options with a clinician (RR 1.57, 95% CI 0.93 to 2.64), but imprecision meant that there was significant uncertainty about both results. AUTHORS' CONCLUSIONS: Very little high quality work has been completed exploring palliative care interventions in advanced dementia. There were only two included studies in this review, with variation in the interventions and in the settings that made it impossible to conduct a meta-analysis of data for any outcome. Thus, we conclude that there is insufficient evidence to assess the effect of palliative care interventions in advanced dementia. The fact that there are six ongoing studies at the time of this review indicates an increased interest in this area by researchers, which is welcome and needed.

The impact of storage temperature and sperm number on the fertility of liquid-stored bull semen.

In Ireland, liquid bull semen is stored at unregulated ambient temperatures, typically at 5×106 spermatozoa per dose, and inseminated within 2.5 days of collection. In Experiment 1, the effect of storage temperature (5, 15, 22, 32°C and fluctuations (Flux) between these temperatures) on progressive motility, viability, acrosomal status, DNA fragmentation and osmotic resistance was assessed. In Experiment 2, the field fertility of liquid semen at 5, 4 and 3×106 spermatozoa per dose, up to Day 2 after collection, was assessed in comparison to frozen-thawed semen at 20×106 spermatozoa per dose (n=35328 inseminations). In Experiment 1, storage at 15°C resulted in the highest progressive motility (PP6 spermatozoa per dose on Day 2 of storage was reduced in comparison to frozen-thawed semen (P<0.01). In conclusion, liquid semen is versatile between storage temperatures of 5 and 22°C, but demonstrates reduced fertility on Day 2 of storage at lower sperm numbers in comparison to frozen-thawed semen.

Pulmonary rehabilitation for chronic obstructive pulmonary disease.

BACKGROUND: Widespread application of pulmonary rehabilitation (also known as respiratory rehabilitation) in chronic obstructive pulmonary disease (COPD) should be preceded by demonstrable improvements in function (health-related quality of life, functional and maximal exercise capacity) attributable to the programmes. This review updates the review reported in 2006. OBJECTIVES: To compare the effects of pulmonary rehabilitation versus usual care on health-related quality of life and functional and maximal exercise capacity in persons with COPD. SEARCH METHODS: We identified additional randomised controlled trials (RCTs) from the Cochrane Airways Group Specialised Register. Searches were current as of March 2014. SELECTION CRITERIA: We selected RCTs of pulmonary rehabilitation in patients with COPD in which health-related quality of life (HRQoL) and/or functional (FEC) or maximal (MEC) exercise capacity were measured. We defined 'pulmonary rehabilitation' as exercise training for at least four weeks with or without education and/or psychological support. We defined 'usual care' as conventional care in which the control group was not given education or any form of additional intervention. We considered participants in the following situations to be in receipt of usual care: only verbal advice was given without additional education; and medication was altered or optimised to what was considered best practice at the start of the trial for all participants. DATA COLLECTION AND ANALYSIS: We calculated mean differences (MDs) using a random-effects model. We requested missing data from the authors of the primary study. We used standard methods as recommended by The Cochrane Collaboration. MAIN RESULTS: Along with the 31 RCTs included in the previous version (2006), we included 34 additional RCTs in this update, resulting in a total of 65 RCTs involving 3822 participants for inclusion in the meta-analysis.We noted no significant demographic differences at baseline between members of the intervention group and those who received usual care. For the pulmonary rehabilitation group, the mean forced expiratory volume at one second (FEV1) was 39.2% predicted, and for the usual care group 36.4%; mean age was 62.4 years and 62.5 years, respectively. The gender mix in both groups was around two males for each female. A total of 41 of the pulmonary rehabilitation programmes were hospital based (inpatient or outpatient), 23 were community based (at community centres or in individual homes) and one study had both a hospital component and a community component. Most programmes were of 12 weeks' or eight weeks' duration with an overall range of four weeks to 52 weeks.The nature of the intervention made it impossible for investigators to blind participants or those delivering the programme. In addition, it was unclear from most early studies whether allocation concealment was undertaken; along with the high attrition rates reported by several studies, this impacted the overall risk of bias.We found statistically significant improvement for all included outcomes. In four important domains of quality of life (QoL) (Chronic Respiratory Questionnaire (CRQ) scores for dyspnoea, fatigue, emotional function and mastery), the effect was larger than the minimal clinically important difference (MCID) of 0.5 units (dyspnoea: MD 0.79, 95% confidence interval (CI) 0.56 to 1.03; N = 1283; studies = 19; moderate-quality evidence; fatigue: MD 0.68, 95% CI 0.45 to 0.92; N = 1291; studies = 19; low-quality evidence; emotional function: MD 0.56, 95% CI 0.34 to 0.78; N = 1291; studies = 19; mastery: MD 0.71, 95% CI 0.47 to 0.95; N = 1212; studies = 19; low-quality evidence). Statistically significant improvements were noted in all domains of the St. George's Respiratory Questionnaire (SGRQ), and improvement in total score was better than 4 units (MD -6.89, 95% CI -9.26 to -4.52; N = 1146; studies = 19; low-quality evidence). Sensitivity analysis using the trials at lower risk of bias yielded a similar estimate of the treatment effect (MD -5.15, 95% CI -7.95 to -2.36; N = 572; studies = 7).Both functional exercise and maximal exercise showed statistically significant improvement. Researchers reported an increase in maximal exercise capacity (mean Wmax (W)) in participants allocated to pulmonary rehabilitation compared with usual care (MD 6.77, 95% CI 1.89 to 11.65; N = 779; studies = 16). The common effect size exceeded the MCID (4 watts) proposed by Puhan 2011(b). In relation to functional exercise capacity, the six-minute walk distance mean treatment effect was greater than the threshold of clinical significance (MD 43.93, 95% CI 32.64 to 55.21; participants = 1879; studies = 38).The subgroup analysis, which compared hospital-based programmes versus community-based programmes, provided evidence of a significant difference in treatment effect between subgroups for all domains of the CRQ, with higher mean values, on average, in the hospital-based pulmonary rehabilitation group than in the community-based group. The SGRQ did not reveal this difference. Subgroup analysis performed to look at the complexity of the pulmonary rehabilitation programme provided no evidence of a significant difference in treatment effect between subgroups that received exercise only and those that received exercise combined with more complex interventions. However, both subgroup analyses could be confounded and should be interpreted with caution. AUTHORS' CONCLUSIONS: Pulmonary rehabilitation relieves dyspnoea and fatigue, improves emotional function and enhances the sense of control that individuals have over their condition. These improvements are moderately large and clinically significant. Rehabilitation serves as an important component of the management of COPD and is beneficial in improving health-related quality of life and exercise capacity. It is our opinion that additional RCTs comparing pulmonary rehabilitation and conventional care in COPD are not warranted. Future research studies should focus on identifying which components of pulmonary rehabilitation are essential, its ideal length and location, the degree of supervision and intensity of training required and how long treatment effects persist. This endeavour is important in the light of the new subgroup analysis, which showed a difference in treatment effect on the CRQ between hospital-based and community-based programmes but no difference between exercise only and more complex pulmonary rehabilitation programmes.

The impact of reminiscence on the quality of life of residents with dementia in long-stay care.

BACKGROUND: There is increasing recognition of the potential use of reminiscence in maintaining or improving the quality of life of people with dementia. Despite being used widely in dementia care, evidence on the effectiveness of reminiscence remains uncertain. AIMS: This study aims to evaluate the effectiveness of a structured education-based reminiscence programme-the Dementia Education Programme Incorporating Reminiscence for Staff-for people with dementia residing in long-stay care settings in Ireland. METHODS: Dementia Education Programme Incorporating Reminiscence for Staff is a two-group, single-blind, cluster randomised trial conducted in long-stay residential care settings in Ireland. The primary outcome was the self-rated quality of life of residents as measured by the Quality of Life-Alzheimer's Disease instrument. RESULTS: Using an intention-to-treat analysis, we found that the estimated effect of the intervention on the quality of life of residents was a non-significant 3.54 (p = 0.1; 95% confidence interval -0.83, 7.90), expressed as the difference in mean improvement between the intervention and control groups. However, the per-protocol analysis yielded a significant effect for the intervention on the quality of life of residents of 5.22 (p = 0.04; 95% confidence interval 0.11, 10.34). CONCLUSIONS: Reminiscence may, in certain circumstances, be an effective care option for people with dementia in long-stay settings with potential to impact positively on the quality of life of residents.

'Seeing me through my memories': a grounded theory study on using reminiscence with people with dementia living in long-term care.

AIMS AND OBJECTIVES: To understand people with dementia, staff and relatives perspectives on reminiscence, its impact on their lives and experience of care and care giving. BACKGROUND: The quality of life of people with dementia living in long-term care is an important question for providers and policymakers. Reminiscence is thought to have potential for increasing resident-staff interaction, thereby contributing to enhanced personhood for people with dementia. Relatively little is known about the effects of reminiscence on people with dementia or staff. DESIGN: This is a grounded theory study. This design was chosen because of its focus on understanding people's behaviour, interaction and response to events. METHODS: In-depth interviews were conducted with residents with dementia (n = 11), relatives (n = 5), healthcare assistants (n = 10), nurses (n = 9) and nurse managers (n = 3). RESULTS: Reminiscence enabled staff to see and know the person beneath the dementia. It acted as … a key revealing the person to staff, enabling them to engage with the person with dementia in a different way. Knowing the person enabled staff to understand (through the lens of the person's past) and sometimes to accommodate the person's current behaviour. CONCLUSION: The theory of 'seeing me (through my memories)' was generated from the data. This theory explains that through reminiscing and engaging with the person with dementia, staff begin to see the person (their personhood) through the mirror of their memories. RELEVANCE TO CLINICAL PRACTICE: This study found that reminiscence enhanced the experience of living in long-term care for residents with dementia and working in long-term care settings for staff.

Developing a structured education reminiscence-based programme for staff in long-stay care facilities in Ireland.

AIMS AND OBJECTIVES: This paper describes the steps used in developing and piloting a structured education programme - the Structured Education Reminiscence-based Programme for Staff (SERPS). The programme aimed to prepare nurses and care assistants to use reminiscence when caring for people with dementia living in long-term care. Reminiscence involves facilitating people to talk or think about their past. BACKGROUND: Structured education programmes are used widely as interventions in randomised controlled trials. However, the process of developing a structured education programme has received little attention relative to that given to evaluating the effectiveness of such programmes. This paper makes explicit the steps followed to develop the SERPS, thereby making a contribution to the methodology of designing and implementing effective structured education programmes. DESIGN: The approach to designing the SERPS was informed by the Van Meijel et al. (2004) model (Journal of Advanced Nursing 48, 84): (1) problem definition, (2) accumulation of building blocks for intervention design, (3) intervention design and (4) intervention validation. METHODS: Grounded theory was used (1) to generate data to shape the 'building blocks' for the SERPS and (2) to explore residents, family and staff's experience of using/receiving reminiscence. RESULTS: Analysis of the pilot data indicated that the programme met its objective of preparing staff to use reminiscence with residents with dementia. Staff were positive both about the SERPS and the use of reminiscence with residents with dementia. CONCLUSIONS: This paper outlines a systematic approach to developing and validating a structured education programme. Participation in a structured education programme is more positive for staff if they are expected to actively implement what they have learnt. Ongoing support during the delivery of the programme is important for successful implementation. RELEVANCE TO CLINICAL PRACTICE: The incorporation of client and professional experience in the design phase is a key strength of this approach to programme design.

Embedding formal and experiential public and patient involvement training in a structured PhD programme: process and impact evaluation.

BACKGROUND: Incorporating Public and Patient Involvement (PPI) into doctoral research is valued by PhD funders and scholars. Providing early career researchers with appropriate training to develop skills to conduct meaningful PPI involvement is important. The Health Research Board (HRB) Collaborative Doctoral Award in MultiMorbidity programme (CDA-MM) embedded formal PPI training in its structured education. The four participating PhD scholars established a PPI panel comprising people living with two or more chronic conditions, presenting an opportunity for experiential PPI training. This study aimed to evaluate the process and impact of embedding PPI training in a structured PhD programme. METHODS: This study was a longitudinal mixed-methods evaluation, conducted over 24 months (June 2020 to June 2022). A process evaluation provided an understanding of how PPI was embedded and explored the experiences of key stakeholders involved. An impact evaluation assessed the impact of embedding PPI training in the programme. Participants included PhD scholars, PPI contributors and PhD supervisors. The data collection and analysis was led by an independent researcher not aligned with the CDA-MM. Data collection methods included five focus groups, individual interviews (n = 6), an impact log, activity logs and group reflections. Qualitative data were analysed using thematic and content analysis and quantitative data analysed using descriptive statistics. RESULTS: Embedding formal and experiential PPI training in a structured PhD programme is feasible. Both approaches to training are fundamental to building PPI capacity. Involvement of an experienced and knowledgeable PPI lead throughout is perceived as critical. The PPI panel approach offered a good example of embedded consultation and worked well in a structured PhD programme, providing PhD scholars with ample opportunities for learning about PPI and its implementation. For PPI contributors, culture was the most important indicator of quality and was positively evaluated. Key roles for PhD supervisors were identified. Embedding formal and experiential PPI training impacted positively on many different aspects of individual PhD research projects and on PhD scholars as researchers. There were positive impacts for PPI contributors and PhD supervisors. CONCLUSIONS: Embedding formal and experiential PPI training in a structured PhD programme is a novel approach. The evaluation has identified a number of lessons that can inform future doctoral programmes seeking to embed formal and experiential PPI training.

Four PhD scholars participated in the CDA-MM. They received training and support from a PPI lead on how to conduct PPI in research. They established a PPI panel of people with two or more ongoing health conditions, to enable PhD scholars to get input from PPI contributors and learn how to do PPI well. An evaluation study was conducted to explore how the PhD scholars conducted PPI, how well it worked, the difference it made and to identify messages for PhD scholars wishing to involve PPI contributors. For the evaluation, the PPI contributors, PhD scholars and PhD supervisors were asked about their experiences and views. For many of the PPI contributors, being part of the CDA-MM PPI panel was their first experience of being involved in PPI. The ongoing support they received from PhD scholars was important. For them, relationships and the way that meetings are conducted matter for doing PPI well. They liked working in small groups and on concrete issues. They found the time they were expected to give was reasonable and within acceptable limits. They preferred in-person meetings. According to PPI contributors, when PPI is done well, it has benefits for the research, particularly ensuring that plain language is used and jargon avoided when researchers communicate with people with two or more ongoing health conditions. PhD scholars benefit from getting the patient perspective and learning how to communicate their research to patients. PPI contributors benefit in many different ways. Some PPI contributors argued that the PPI advisory panel worked so well in the CDA-MM that no changes were needed, whereas others would like to explore different ways of being involved in research.

A protocol for the evaluation of the process and impact of embedding formal and experiential Public and Patient Involvement training in a structured PhD programme.

BACKGROUND: Incorporating Public and Patient Involvement (PPI) into doctoral research is valued by PhD scholars. The importance of providing early career researchers with appropriate education and training to develop skills to conduct meaningful involvement has been articulated. The Collaborative Doctoral Award in MultiMorbidity (CDA-MM) PhD programme embedded formal PPI training as a postgraduate education component. Four PhD scholars taking part in the CDA-MM established a PPI panel comprising people, and carers of people, living with multimorbidity (≥2 chronic conditions), presenting an opportuning for experiential PPI training. The proposed study aims to evaluate the process and impact of formal and experiential PPI training during a PhD programme. DESIGN: Embedding PPI training in a PhD programme is a novel approach. This evaluation will include a process evaluation to provide an understanding of the workings of the PPI panel and explore the experiences of key stakeholders involved, and an impact evaluation to assess the impact of embedding PPI training in a PhD programme. This study is a longitudinal mixed-methods evaluation, conducted over 24 months. Participants include PhD scholars, PPI contributors and PhD supervisors. An independent researcher not aligned with the CDA-MM will lead the evaluation. Data collection methods include focus groups, individual interviews, an impact log and group reflections. Qualitative data will be analysed using thematic and content analysis and quantitative data will be analysed using descriptive statistics. DISCUSSION: This evaluation will report the learnings from embedding formal and experiential PPI training and education across a PhD programme.

COVID-19: Public and patient involvement, now more than ever.

The research community is responding with speed to the COVID-19 pandemic, with rapid response mechanisms to fund research, shortened application turnaround times, and expedited research ethics processes. Public and patient involvement (PPI) is under pressure in this rapid response research, where it is easy for researchers and funders to dismiss PPI as non-essential, an added extra, a "nice to have".  In this open letter, we, researchers and PPI contributors, argue that PPI is important, now more than ever. The pandemic is impacting everyone in society, with normal rules of engagement discarded. The solution to overcoming this virus will come from many different sources and many changes will emerge to healthcare delivery and to how we live our lives. It is essential that the research to find solutions is shaped by all who will be impacted: the public and the patient must be central contributors and their voice must be hear.

Quality, scope and reporting standards of randomised controlled trials in Irish Health Research: an observational study.

BACKGROUND: Despite efforts to improve the accuracy and transparency of the design, conduct, and reporting of randomised controlled trials (RCTs), deficiencies remain. Such deficiencies contribute to significant, avoidable waste of health research investment and impede reproducibility. This study aimed to synthesise and critically analyse changes over time in the conduct and reporting of internationally published evidence on patient and/or population health-oriented RCTs conducted in one country. METHODS: This observational study drew on systematic review methods. We searched six databases for published RCTs (database inception to December 2018) where ≥ 80% of participants were recruited in the Republic of Ireland. RCTs of interventions targeted at patients, providers and/or policy makers intended to improve health, healthcare or health research were included. For each study, screening, data extraction and methodological quality appraisal were conducted by one member of the author team. RESULTS: From 17,560 titles and abstracts, 752 unique RCTs were published in 745 papers between 1968 and 2018, with a steady year-on-year increase since 1968. The number of participants was in the range of 2-8628. The majority were parallel design (86%) and classified as treatment evaluation. Of the 418 RCTs published since the introduction of mandatory clinical trial registration by the International Committee of Medical Journal Editors in 2005, 32% (n = 134) provided a trial registration number. This increased to 47% when taking studies published between 2013 and 2018 (n = 232). Since the 1996 publication of the CONSORT statement, 16% of included RCTs made specific reference to a standardised reporting guideline and this increased to 31% for more recent studies published between 2013 and 2018. Overall, 7% (n = 53) of studies referred to a published study protocol, increasing to 20% for studies published between 2013 and 2018. CONCLUSION: Evidence from this single-country study of RCTs published in the international literature suggests that both the number overall, the number registered and the number referencing reporting guidelines have increased steadily over time. Despite widespread endorsement of reporting standards, reporting of RCTs remains suboptimal in domains such as compliance with the CONSORT statement and prospective trial registration. Researchers, funders and journal editors, nationally and internationally, should continue to focus on improving reporting and examining avoidable waste of health research investment.

Minding the gap: identifying values to enable public and patient involvement at the pre-commencement stage of research projects.

BACKGROUND: The University College Dublin (UCD) Public and Patient Invovlement (PPI) ignite program is focused on embedding PPI in health and social care related research, education and training, professional practice and administration. During a PPI knowledge sharing event challenges were noted during the pre-commencement stage of research projects. This stage includes the time before a research projects/partnership starts or when funding is being applied for. As a response, we agreed there was a need to spend time developing a values-based approach to be used from the pre-commencement of PPI projects and partnerships. Values are deeply held ideals that people consider to be important. They are vital in shaping our attitudes and motivating our choices and behaviours. METHODS: Using independent facilitators, we invited a diverse group of participants to a full-day workshop in February. During the workshop, the concept of a values statement and values-based approaches was introduced. The group via a majority consensus, agreed on a core set of values and a shared understanding of them. After the workshop, a draft was shared with participants for further comment and final agreement. RESULTS: The workshop had 22 people representing experts by experience, PPI charity partners, funders, academics and national PPI Ignite partners. The group via consensus identified four values of respect, openness, reciprocity and flexibility for the pre-commencement stage. A frequently reported experience of PPI partners was that some felt that the pre-commencement activities appeared at times like a performance; an act that had to be completed in order to move to the next stage rather than a genuine interest in a mutually beneficial partnership. Being open and transparent with all invovled that the funding application may not be successful was stressed. Another important feature related to 'openness' was the 'spaces' and 'places' in which meetings between partners could occur in an accessible and equitable way. The issue of 'space' is particularly critical for the involvement of seldom heard groups. The benefits of the research are often clear for academics, but for PPI partners, these are often less certain. To achieve reciprocity, academic and PPI partners need to engage in a timely, repeated and transparent dialogue to achieve beneficial outcomes for all stakeholders. Being open to new inputs and differing modes of knowledge and ideas was also stressed. For some, this will require a change in attitudes and behaviours and should result in more collective decision making. Several areas were identified using the four values. CONCLUSIONS: This work via majority consensus identified four values of respect, openness, reciprocity, and flexibility for the pre-commencement stage. These values should be used to support inclusive, effective and collective PPI across all stages of involvement. We hope this work will stimulate further action in this area. In particular, we would welcome the evaluation of these values involving diverse PPI groups.

Influence of bull age, ejaculate number, and season of collection on semen production and sperm motility parameters in Holstein Friesian bulls in a commercial artificial insemination centre.

In the current era of genomic selection, there is an increased demand to collect semen from genomically selected sires at a young age. The objective of this study was to assess the effect of bull age, ejaculate number, and season of collection on semen production (ejaculate volume, sperm concentration, and total sperm number; TSN) and sperm motility (prefreeze and post-thaw total and gross motility) parameters in Holstein Friesian bulls in a commercial artificial insemination (AI) center. The study involved the interrogation of a large dataset collected over a 4-yr period, (n = 8,983 ejaculates; n = 176 Holstein Friesian bulls aged between 9 mo and 8 yr). Bulls aged less than 1 yr had the poorest semen production and sperm motility values for all parameters assessed compared with bulls older than 1 yr (P < 0.01). First ejaculates had greater semen production and greater prefreeze motility values than second consecutive ejaculates (P < 0.01), but despite this, there was no difference in post-thaw motility. When subsequent ejaculates were collected from bulls aged less than 1 yr, semen production and sperm motility did not differ compared with mature bulls. Semen collected in winter was poorest in terms of sperm concentration and TSN, but best in terms of post-thaw motility (P < 0.01). In conclusion, second ejaculates can be collected, particularly from bulls aged less than 1 yr, without a significant decrease in post-thaw sperm motility, thus may be a useful strategy to increase semen availability from young genomically selected AI bulls in high demand.

Long-term cost effectiveness of cardiac secondary prevention in primary care in the Republic of Ireland and Northern Ireland.

While cardiac secondary prevention in primary care is established practice, little is known about its long-term cost effectiveness. This study examines the cost effectiveness of a secondary prevention intervention in primary care in the Republic of Ireland and Northern Ireland over 6 years. An economic evaluation, based on a cluster randomised controlled trial of 903 patients with heart disease, was conducted 4.5 years after the intervention ceased to be delivered. Patients originally randomised to the control received usual practice while those randomised to the intervention received a tailored care package over the 1.5-year delivery period. Data on healthcare costs and quality adjusted life expectancy were used to undertake incremental cost utility analysis. Multilevel regression was used to estimate mean cost effectiveness and uncertainty was examined using cost effectiveness acceptability curves. At 6 years, there was a divergence in the results across jurisdictions. While the probability of the intervention being cost effective in the Republic of Ireland was 0.434, 0.232, 0.180, 0.150, 0.115 and 0.098 at selected threshold values of €5000, €15,000, €20,000, €25,000, €35,000 and €45,000, respectively, all equivalent probabilities for Northern Ireland equalled 1.000. Our findings suggest that the intervention in its current format is likely to be more cost effective than usual general practice care in Northern Ireland, but this is not the case in the Republic of Ireland.

Supportive text messages for patients with alcohol use disorder and a comorbid depression: a protocol for a single-blind randomised controlled aftercare trial.

INTRODUCTION: Alcohol use disorders (AUDs) and mood disorders commonly co-occur, and are associated with a range of negative outcomes for patients. Mobile phone technology has the potential to provide personalised support for such patients and potentially improve outcomes in this difficult-to-treat cohort. The aim of this study is to examine whether receiving supporting SMS text messages, following discharge from an inpatient dual diagnosis treatment programme, has a positive impact on mood and alcohol abstinence in patients with an AUD and a comorbid mood disorder. METHODS AND ANALYSIS: The present study is a single-blind randomised controlled trial. Patients aged 18-70 years who meet the criteria for both alcohol dependency syndrome/alcohol abuse and either major depressive disorder or bipolar disorder according to the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders IV Axis I will be randomised to receive twice-daily supportive SMS text messages for 6 months plus treatment as usual, or treatment as usual alone, and will be followed-up at 3, 6, 9 and 12 months postdischarge. Primary outcome measures will include changes from baseline in cumulative abstinence duration, which will be expressed as the proportion of days abstinent from alcohol in the preceding 90 days, and changes from baseline in Beck Depression Inventory scores. ETHICS AND DISSEMINATION: The trial has received full ethical approval from the St. Patrick's Hospital Research Ethics Committee (protocol 13/14). Results of the trial will be disseminated through peer-reviewed journal articles and at academic conferences. TRIAL REGISTRATION NUMBER: NCT02404662; Pre-results.