Portiuncula Hospital

INTRODUCTION: The prevalence of frailty at population level is unclear. We examined this in population-based studies, investigating sources of heterogeneity. METHODS: PubMed, Embase, CINAHL and Cochrane Library databases were searched for observational population-level studies published between 1 January 1998 and 1 April 2020, including individuals aged ≥50 years, identified using any frailty measure. Prevalence estimates were extracted independently, assessed for bias and analysed using a random-effects model. RESULTS: In total, 240 studies reporting 265 prevalence proportions from 62 countries and territories, representing 1,755,497 participants, were included. Pooled prevalence in studies using physical frailty measures was 12% (95% CI = 11-13%; n = 178), compared with 24% (95% CI = 22-26%; n = 71) for the deficit accumulation model (those using a frailty index, FI). For pre-frailty, this was 46% (95% CI = 45-48%; n = 147) and 49% (95% CI = 46-52%; n = 29), respectively. For physical frailty, the prevalence was higher among females, 15% (95% CI = 14-17%; n = 142), than males, 11% (95% CI = 10-12%; n = 144). For studies using a FI, the prevalence was also higher in females, 29% (95% CI = 24-35%; n = 34) versus 20% (95% CI = 16-24%; n = 34), for males. These values were similar for pre-frailty. Prevalence increased according to the minimum age at study inclusion. Analysing only data from nationally representative studies gave a frailty prevalence of 7% (95% CI = 5-9%; n = 46) for physical frailty and 24% (95% CI = 22-26%; n = 44) for FIs. CONCLUSIONS: Population-level frailty prevalence varied by classification and sex. Data were heterogenous and limited, particularly from nationally representative studies making the interpretation of differences by geographic region challenging. Common methodological approaches to gathering data are required to improve the accuracy of population-level prevalence estimates. PROTOCOL REGISTRATION: PROSPERO-CRD42018105431.

The first work of its kind, The History of Medications for Women: Materia medica woman is a richly detailed, far-ranging illustrated history of medications for women in all the great cultures and civilizations, from ancient times to the present. Compiled by an acclaimed author of medical history literature, this is the only book that extends from the earliest uses of ergometrine, lettuce, and mummy medicine, through the history of women's medications in ancient Assyria and Egypt, and into the 16th through 20th centuries. With the main sections organized by origin and timeline, the book contains lists of medications used by women from earliest times to the present accompanied by historically-based text. The author includes botanical, chemical, pharmacalogical, and therapeutic details where appropriate, as well as extensive quotations from both contemporary and old, rare books. The text is complemented with the history of obstetrics and gynecology, along with short biographies and illustrations. Additionally, the author presents a unique fund of hard-to-find information in sections devoted to topics such as anesthesia and analgesia, antiseptics, antibiotics and chemotherapy, blood transfusion and Rhesus disease, eclampsia, family planning, menopause, and uterine stimulants. Interesting and thought-provoking, The History of Medications for Women will not only provide an enjoyable read, but will allow you to appreciate the past and look at the future with a new perspective.

Thiazide diuretics, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers all cause reactive rises in plasma renin activity. We hypothesized that renin inhibition with aliskiren would prevent this reactive rise and also enhance blood pressure lowering. In 3 open-label studies in which blood pressure was assessed with ambulatory measurement, aliskiren was administered to patients with mild-to-moderate hypertension in combination with hydrochlorothiazide (n=23), ramipril (n=21), or irbesartan (n=23). In the diuretic combination study, the addition of 25 mg of hydrochlorothiazide to 150 mg of aliskiren daily for 3 weeks significantly lowered daytime pressure, compared with aliskiren monotherapy (systolic/diastolic mean change from baseline [SEM]: daytime: -18.4 [2.1]/ -10.6 [1.7] versus -10.4 [1.8]/-5.8 [1.4]; nighttime: -15.6 [2.7]/-8.1 [1.8] versus -8.8 [2.9]/-5.0 [2.2]). In the angiotensin-converting enzyme inhibitor combination study, the addition of 75 or 150 mg of aliskiren to 5 mg of ramipril alone for 3 weeks further lowered both daytime and nighttime pressures compared with ramipril monotherapy (daytime: -10.5 [2.9]/-8.1 [2.1] and -14 [3.7]/-8.7 [2.3] versus -6.1 [2.4]/-5.9 [1.5]; nighttime: -8.1 [2.6]/-5.3 [2.4] and -9.6 [3.4]/-5.3 [2.4] versus -2 [2.3]/-0.7 [2.2]). In the angiotensin receptor blocker combination study, the addition of 75 or 150 mg of aliskiren to 150 mg of irbesartan alone, for 3 weeks, resulted in significantly lower nighttime pressures compared with irbesartan monotherapy (daytime: -14.8 [2]/-8.2 [1.3] and -13.3 [1.6]/-6.8 [0.9] versus -11.4 [1.6]/-6.5 [1.1]; nighttime: -16.1 [2.4]/-8.6 [1.7] and -13.2 [2.7]/-7.2 [1.9] versus -9.0 [2.5]/-4.7 [1.9]). Aliskiren (150 mg) alone significantly inhibited plasma renin activity by 65% (P<0.0001). Ramipril and irbesartan monotherapy caused 90% and 175% increases in plasma renin activity, respectively. By contrast, when aliskiren was coadministered with hydrochlorothiazide, ramipril, or irbesartan, plasma renin activity did not increase but remained similar to baseline levels or was decreased (combination therapy versus untreated; median [interquartile range]; aliskiren and hydrochlorothiazide: 0.4 [0.2 to 1.1] versus 0.7 [0.5 to 1.3]; ramipril and aliskiren: 0.5 [0.3 to 0.9] versus 0.6 [0.5 to 0.8]; irbesartan and aliskiren: 0.4 [0.2 to 0.9] versus 0.6 [0.4 to 0.9]). These results suggest that renin inhibition with aliskiren in these combinations increases renin-angiotensin system suppression, improves 24-hour blood pressure control, and may ultimately provide better end-organ protection in patients with hypertension.

COVID-19 is also manifested with hypercoagulability, pulmonary intravascular coagulation, microangiopathy, and venous thromboembolism (VTE) or arterial thrombosis. Predisposing risk factors to severe COVID-19 are male sex, underlying cardiovascular disease, or cardiovascular risk factors including noncontrolled diabetes mellitus or arterial hypertension, obesity, and advanced age. The VAS-European Independent Foundation in Angiology/Vascular Medicine draws attention to patients with vascular disease (VD) and presents an integral strategy for the management of patients with VD or cardiovascular risk factors (VD-CVR) and COVID-19. VAS recommends (1) a COVID-19-oriented primary health care network for patients with VD-CVR for identification of patients with VD-CVR in the community and patients' education for disease symptoms, use of eHealth technology, adherence to the antithrombotic and vascular regulating treatments, and (2) close medical follow-up for efficacious control of VD progression and prompt application of physical and social distancing measures in case of new epidemic waves. For patients with VD-CVR who receive home treatment for COVID-19, VAS recommends assessment for (1) disease worsening risk and prioritized hospitalization of those at high risk and (2) VTE risk assessment and thromboprophylaxis with rivaroxaban, betrixaban, or low-molecular-weight heparin (LMWH) for those at high risk. For hospitalized patients with VD-CVR and COVID-19, VAS recommends (1) routine thromboprophylaxis with weight-adjusted intermediate doses of LMWH (unless contraindication); (2) LMWH as the drug of choice over unfractionated heparin or direct oral anticoagulants for the treatment of VTE or hypercoagulability; (3) careful evaluation of the risk for disease worsening and prompt application of targeted antiviral or convalescence treatments; (4) monitoring of D-dimer for optimization of the antithrombotic treatment; and (5) evaluation of the risk of VTE before hospital discharge using the IMPROVE-D-dimer score and prolonged post-discharge thromboprophylaxis with rivaroxaban, betrixaban, or LMWH.

Increasing pressure on limited healthcare resources has necessitated the development of measures promoting early discharge and avoiding inappropriate hospital (re)admission. This systematic review examines the evidence for interventions in acute hospitals including (i) hospital-patient discharge to home, community services or other settings, (ii) hospital discharge to another care setting, and (iii) reduction or prevention of inappropriate hospital (re)admissions. Academic electronic databases were searched from 2005 to 2018. In total, ninety-four eligible papers were included. Interventions were categorized into: (1) pre-discharge exclusively delivered in the acute care hospital, (2) pre- and post-discharge delivered by acute care hospital, (3) post-discharge delivered at home and (4) delivered only in a post-acute facility. Mixed results were found regarding the effectiveness of many types of interventions. Interventions exclusively delivered in the acute hospital pre-discharge and those involving education were most common but their effectiveness was limited in avoiding (re)admission. Successful pre- and post-discharge interventions focused on multidisciplinary approaches. Post-discharge interventions exclusively delivered at home reduced hospital stay and contributed to patient satisfaction. Existing systematic reviews on tele-health and long-term care interventions suggest insufficient evidence for admission avoidance. The most effective interventions to avoid inappropriate re-admission to hospital and promote early discharge included integrated systems between hospital and the community care, multidisciplinary service provision, individualization of services, discharge planning initiated in hospital and specialist follow-up.

Clostridium difficile is the principal pathogen associated with hospital-acquired acute diarrheal disease. We have evaluated the performances of six approaches for diagnosis of C. difficile-associated diarrhea (CDAD). Consecutive stool specimens (n = 200) from 133 patients were examined by cytotoxin assay, by culture of C. difficile on cycloserine-cefoxitin-fructose agar, and by toxin detection using four rapid immunoassay systems (Oxoid Toxin A test, ImmunoCard Toxin A test, TechLab Tox A/B II test, and Premier Toxins A&B test). A diagnosis of CDAD was established for 35 (27%) patients (representing 29% of specimens). The adjusted sensitivity and specificity of the methods were, respectively, 98 and 99% for the cytotoxin assay, 54 and 99% for ImmunoCard, 50 and 98% for Oxoid, 79 and 98% for TechLab, 80 and 98% for Premier, and 57 and 100% for culture. The TechLab and Premier assays are acceptable tests for diagnosis of CDAD but are not equivalent to the cytotoxin assay.

BACKGROUND: Studies have shown disparate results in relation to the role of plasma concentrations of cell adhesion molecules in atherosclerosis. Moreover, the differentiation of primary vs secondary alterations of these markers, in response to myocardial injury, has not been clear. We measured specific soluble cell adhesion molecules and inflammatory markers in men admitted acutely with chest pain and compared them to healthy controls. METHODS AND RESULTS: We prospectively studied men (total n=241), admitted acutely with chest pain (7.4+/-9.4 h, 71% within 10 h), unstable angina (n=67), acute myocardial infarction (n=47) and chest pain without ischaemic heart disease (n=45) and compared them with a stratified sample of randomly selected healthy controls (n=82). Soluble intercellular adhesion molecule (sICAM-1), endothelial selectin, vascular cell adhesion molecule, interleukin-6 and C-reactive protein were measured by ELISA and P-selectin expression by flow cytometry. Multiple regression analysis was used to control for the impact of classical risk factors. At baseline ICAM-1, interleukin-6 and C-reactive protein were significantly elevated in patient groups whereas no difference in vascular cell adhesion molecule or endothelial selectin was found. At 3 month follow-up, ICAM-1 level was unchanged in ischaemic heart disease patients. In all groups C-reactive protein and interleukin-6 levels were lower at review. ICAM-1 levels at follow-up were higher in ischaemic heart disease groups (but not in chest pain without ischaemic heart disease) relative to controls and remained so only in the unstable angina group following regression. sICAM-1, interleukin-6 and C-reactive protein strongly correlated with smoking. In the acute phase, ICAM-1 was confounded by smoking following regression and C-reactive protein and interleukin-6 remained significant in both ischaemic heart disease groups after multiple regression. There was no relationship to events which occurred in 23% of ischaemic heart disease patients (further acute myocardial infarction 5.3%, sudden cardiac death 0.9% or recurrent angina 16.7%). CONCLUSION: We found an inflammatory response with higher sICAM-1, interleukin-6 and C-reactive protein in patients presenting soon after developing an acute coronary syndrome. As sICAM-1 was not affected by the acute event this plasma marker may be an important risk factor for the development of the acute coronary syndrome, particularly unstable angina.

Importance: Gestational diabetes is a common complication of pregnancy and the optimal management is uncertain. Objective: To test whether early initiation of metformin reduces insulin initiation or improves fasting hyperglycemia at gestation weeks 32 or 38. Design, Setting, and Participants: Double-blind, placebo-controlled trial conducted in 2 centers in Ireland (one tertiary hospital and one smaller regional hospital). Participants were enrolled from June 2017 through September 2022 and followed up until 12 weeks' postpartum. Participants comprised 510 individuals (535 pregnancies) diagnosed with gestational diabetes based on World Health Organization 2013 criteria. Interventions: Randomized 1:1 to either placebo or metformin (maximum dose, 2500 mg) in addition to usual care. Main Outcomes And Measures: The primary outcome was a composite of insulin initiation or a fasting glucose level of 5.1 mmol/L or greater at gestation weeks 32 or 38. Results: Among 510 participants (mean age, 34.3 years), 535 pregnancies were randomized. The primary composite outcome was not significantly different between groups and occurred in 150 pregnancies (56.8%) in the metformin group and 167 pregnancies (63.7%) in the placebo group (between-group difference, -6.9% [95% CI, -15.1% to 1.4%]; relative risk, 0.89 [95% CI, 0.78-1.02]; P = .13). Of 6 prespecified secondary maternal outcomes, 3 favored the metformin group, including time to insulin initiation, self-reported capillary glycemic control, and gestational weight gain. Secondary neonatal outcomes differed by group, with smaller neonates (lower mean birth weights, a lower proportion weighing >4 kg, a lower proportion in the >90% percentile, and smaller crown-heel length) in the metformin group without differences in neonatal intensive care needs, respiratory distress requiring respiratory support, jaundice requiring phototherapy, major congenital anomalies, neonatal hypoglycemia, or proportion with 5-minute Apgar scores less than 7. Conclusion and relevance: Early treatment with metformin was not superior to placebo for the composite primary outcome. Prespecified secondary outcome data support further investigation of metformin in larger clinical trials. Trial Registration: ClinicalTrials.gov Identifier: NCT02980276; EudraCT: 2016-001644-19.

Abstract Aim The aim of this systematic review was to evaluate the clinical characteristics of COVID‐19 in neonates and children under one year of age. Methods A systematic literature review of the MEDLINE, PubMed, CINAHL, Embase and EBSCO databases was carried out for studies from January 1, 2020, to April 7, 2020. We included all papers that addressed clinical manifestations, laboratory results, imaging findings and outcomes in infants and neonates. Results Our search identified 77 peer‐reviewed papers, and 18 papers covering 160 infants were reviewed. One paper was from Vietnam, and the other 17 were from China: eight were cross‐sectional studies, eight were case reports, one was a case series, and one was a prospective cohort study. The most common clinical symptoms were fever (54%) and cough (33%). Most infants were treated symptomatically, with frequent use of various empirical medications. Infants and neonates tended to have more severe COVID‐19 disease than older children: 11 (7%) were admitted to intensive care and one infant died. The mortality rate was 0.006%, with favourable outcomes in most cases. Conclusion Infants and neonates were more vulnerable to more severe COVID‐19 disease than older children, but morbidity and mortality were low.

BACKGROUND: Negative pressure wound therapy (NPWT) is a promising advance in the management of closed surgical incisions. NPWT application induces several effects locally within the wound including reduced lateral tension and improving lymphatic drainage. As a result, NPWT may improve wound healing and reduce surgical site complications. We aim to evaluate the efficacy of prophylactic application of NPWT in preventing surgical site complications for closed incisions in breast surgery. METHODS: This systematic review was reported according to PRISMA guidelines. The protocol was published in PROSPERO (CRD42018114625). Medline, Embase, CINAHL and Cochrane Library databases were searched for studies which compare the efficacy of NPWT versus non-NPWT dressings for closed incisions in breast surgery. Specific outcomes of interest were total wound complications, surgical site infection (SSI), seroma, haematoma, wound dehiscence and necrosis. RESULTS: Seven studies (1500 breast incisions in 904 patients) met the inclusion criteria. NPWT was associated with a significantly lower rate of total wound complications [odds ratio (OR) 0.36; 95% CI 0.19-069; P = 0.002], SSI (OR 0.45; 95% CI 0.24-0.86; P = 0.015), seroma (OR 0.28; 95% CI 0.13-0.59; P = 0.001), wound dehiscence (OR 0.49; 95% CI 0.32-0.72; P < 0.001) and wound necrosis (OR 0.38; 95% CI 0.19-0.78; P = 0.008). There was no significant difference in haematoma rate (OR 0.8; 95% CI 0.19-3.2; P = 0.75). Statistically significant heterogeneity existed for total wound complications, but no other outcomes. CONCLUSION: Compared with conventional non-NPWT dressings, prophylactic application of NPWT is associated with significantly fewer surgical site complications including SSI, seroma, wound dehiscence and wound necrosis for closed breast incisions.

AIM: The aim of this study was to investigate the microbiology of secondary bacterial peritonitis due to appendicitis and the appropriateness of current antimicrobial practice in one institution. METHODS: A 14-year retrospective single-centre study of 69 consecutive paediatric patients (age 1-14 years) with appendicitis-related peritonitis and positive peritoneal specimen cultures was conducted. Post-operative outcomes, microbiology and antibiotic susceptibility of peritoneal isolates were analysed in all patients. RESULTS: Escherichia coli was identified in 56/69 (81 %) peritoneal specimens; four isolates were resistant to amoxicillin-clavulanate, and one other isolate was resistant to gentamicin. Anaerobes were identified in 37/69 (54 %) peritoneal specimens; two anaerobic isolates were resistant to amoxicillin-clavulanate and one isolate was resistant to metronidazole. Pseudomonas aeruginosa was identified in 4/69 (6 %) peritoneal specimens, and all were susceptible to gentamicin. Streptococcal species (two Group F streptococci and three β-haemolytic streptococci) were identified in 5/69 (7 %) specimens, and all were susceptible to amoxicillin-clavulanate. Combination therapy involving amoxicillin-clavulanate and aminoglycoside is appropriate empirical treatment in 68/69 (99 %) patients. Addition of metronidazole to this regime would provide 100 % initial empirical coverage. Inadequate initial empiric antibiotic treatment and the presence of amoxicillin-clavulanate resistant E. coli were independent predictors of the post-operative infectious complications observed in 14/69 (20 %) patients. CONCLUSION: E. coli and mixed anaerobes are the predominant organisms identified in secondary peritonitis from appendicitis in children. Inadequate initial empirical antibiotic and amoxicillin-clavulanate resistant E. coli may contribute to increased post-operative infectious complications. This study provides evidence-based information on choice of combination therapy for paediatric appendicitis-related bacterial peritonitis.

BACKGROUND: Peripheral arterial disease (PAD), caused by narrowing of the arteries in the limbs, is increasing in incidence and prevalence as our population is ageing and as diabetes is becoming more prevalent. PAD can cause pain in the limbs while walking, known as intermittent claudication, or can be more severe and cause pain while at rest, ulceration, and ultimately gangrene and limb loss. This more severe stage of PAD is known as 'critical limb ischaemia'. Treatments for PAD include medications that help to reduce the increased risk of cardiovascular events and help improve blood flow, as well as endovascular or surgical repair or bypass of the blocked arteries. However, many people are unresponsive to medications and are not suited to surgical or endovascular treatment, leaving amputation as the last option. Gene therapy is a novel approach in which genetic material encoding for proteins that may help increase revascularisation is injected into the affected limbs of patients. This type of treatment has been shown to be safe, but its efficacy, especially regarding ulcer healing, effects on quality of life, and other symptomatic outcomes remain unknown. OBJECTIVES: To assess the effects of gene therapy for symptomatic peripheral arterial disease. SEARCH METHODS: The Cochrane Vascular Information Specialist searched Cochrane CENTRAL, the Cochrane Vascular Specialised Register, MEDLINE Ovid, Embase Ovid, CINAHL, and AMED, along with trials registries (all searched 27 November 2017). We also checked reference lists of included studies and systematic reviews for further studies. SELECTION CRITERIA: We included randomised and quasi-randomised studies that evaluated gene therapy versus no gene therapy in people with PAD. We excluded studies that evaluated direct growth hormone treatment or cell-based treatments. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, performed quality assessment, and extracted data from the included studies. We collected pertinent information on each study, as well as data for the outcomes of amputation-free survival, ulcer healing, quality of life, amputation, all-cause mortality, ankle brachial index, symptom scores, and claudication distance. MAIN RESULTS: We included in this review a total of 17 studies with 1988 participants (evidence current until November 2017). Three studies limited their inclusion to people with intermittent claudication, 12 limited inclusion to people with varying levels of critical limb ischaemia, and two included people with either condition. Study investigators evaluated many different types of gene therapies, using different protocols. Most studies evaluated growth factor-encoding gene therapy, with six studies using vascular endothelial growth factor (VEGF)-encoding genes, four using hepatocyte growth factor (HGF)-encoding genes, and three using fibroblast growth factor (FGF)-encoded genes. Two studies evaluated hypoxia-inducible factor 1-alpha (HIF-1α) gene therapy, one study used a developmental endothelial locus-1 gene therapy, and the final study evaluated a stromal cell-derived factor-1 (SDF-1) gene therapy. Most studies reported outcomes after 12 months of follow-up, but follow-up ranged from three months to two years.Overall risk of bias varied between studies, with many studies not providing sufficient detail for adequate determination of low risk of bias for many domains. Two studies did not utilise a placebo control, leading to risk of performance bias. Several studies reported in previous protocols or in their Methods sections that they would report on certain outcomes for which no data were then reported, increasing risk of reporting bias. All included studies reported sponsorships from corporate entities that led to unclear risk of other bias. The overall quality of evidence ranged from moderate to very low, generally as the result of heterogeneity and imprecision, with few or no studies reporting on outcomes.Evidence suggests no clear differences for the outcomes of amputation-free survival, major amputation, and all-cause mortality between those treated with gene therapy and those not receiving this treatment (all moderate-quality evidence). Low-quality evidence suggests improvement in complete ulcer healing with gene therapy (odds ratio (OR) 2.16, 95% confidence interval (CI) 1.02 to 4.59; P = 0.04). We could not combine data on quality of life and can draw no conclusions at this time regarding this outcome (very low-quality evidence). We included one study in the meta-analysis for ankle brachial index, which showed no clear differences between treatments, but we can draw no overall association (low-quality evidence). We combined in a meta-analysis pain symptom scores as assessed by visual analogue scales from two studies and found no clear differences between treatment groups (very low-quality evidence). We carried out extensive subgroup analyses by PAD classification, dosage schedule, vector type, and gene used but identified no substantial differences. AUTHORS' CONCLUSIONS: Moderate-quality evidence shows no clear differences in amputation-free survival, major amputation, and all-cause mortality between those treated with gene therapy and those not receiving gene therapy. Some evidence suggests that gene therapy may lead to improved complete ulcer healing, but this outcome needs to be explored with improved reporting of the measure, such as decreased ulcer area in cm², and better description of ulcer types and healing. Further standardised data that are amenable to meta-analysis are needed to evaluate other outcomes such as quality of life, ankle brachial index, symptom scores, and claudication distance.

BACKGROUND: The Ouabain and Adducin for Specific Intervention on Sodium in Hypertension (OASIS-HT) Trial was a phase-2 dose-finding study of rostafuroxin, a digitoxygenin derivative, which selectively antagonizes the effects of endogenous ouabain (EO) on Na+,K+-ATPase and mutated adducin. Rostafuroxin lowered blood pressure (BP) in some animal models and in humans. METHODS: OASIS-HT consisted of 5 concurrently running double-blind cross-over studies. After 4 weeks without treatment, 435 patients with uncomplicated systolic hypertension (140-169 mm Hg) were randomized to rostafuroxin (0.05, 0.15, 0.5, 1.5 or 5.0 mg/d) or matching placebo, each treatment period lasting 5 weeks. The primary endpoint was the reduction in systolic office BP. Among the secondary endpoints were diastolic office BP, 24-h ambulatory BP, plasma EO concentration and renin activity, 24-h urinary sodium and aldosterone excretion, and safety. ANOVA considered treatment sequence (fixed effect), subjects nested within sequence (random), period (fixed), and treatment (fixed). RESULTS: Among 410 analyzable patients (40.5% women; mean age, 48.4 years), the differences in the primary endpoint (rostafuroxin minus placebo) ranged from -0.18 mm Hg (P = 0.90) on 0.15 mg/d rostafuroxin to 2.72 mm Hg (P = 0.04) on 0.05 mg/d. In the 5 dosage arms combined, the treatment effects averaged 1.30 mm Hg (P = 0.03) for systolic office BP; 0.70 mm Hg (P = 0.08) for diastolic office BP; 0.36 mm Hg (P = 0.49) for 24-h systolic BP; and 0.05 mm Hg (P = 0.88) for 24-h diastolic BP. In the 2 treatment groups combined, systolic (-1.36 mm Hg) and diastolic (-0.97 mm Hg) office BPs decreased from week 5 to 10 (P for period effect ≤ 0.028), but carry-over effects were not significant (P ≥ 0.11). All other endpoints were not different on rostafuroxin and placebo. Minor side-effects occurred with similarly low frequency on rostafuroxin and placebo. CONCLUSIONS: In 5 concurrently running double-blind cross-over studies rostafuroxin did not reduce BP at any dose. TRIAL REGISTRATION: ClinicalTrials (NCT): NCT00415038.

WHAT IS KNOWN ABOUT THE SUBJECT?: The Advancing Recovery in Ireland (ARI) project (Health Service Executive, 2012) promotes recovery-orientated services. A previous study of Irish mental health practitioners (Cleary & Dowling ) identified the need to improve knowledge and attitudes towards recovery. To facilitate implementation of ARI and monitor progress, this study provided a 'benchmark' of current knowledge and attitudes to recovery. WHAT THIS STUDY ADDS TO EXISTING KNOWLEDGE?: The study provides important baseline information on recovery knowledge and attitudes which can be used to assess the impact of the ARI Project. It also provides valuable information that can be compared to recovery approaches employed in other countries. Despite the increased emphasis on recovery in Ireland, knowledge and attitudes of health care practitioners towards recovery remain relatively unchanged between 2007 and 2013. Working in dual settings, being a non-nurse, and training was associated with better RKI scores. Training appears to be the strongest factor in predicting better recovery knowledge. The findings suggest that knowledge levels and attitude changes following education may not be sustained over time and ongoing training may be required. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: There is considerable scope to improve recovery knowledge. Key recommendations include the need for more recovery training, evaluate whether training translates into clinical practice, using 'Recovery Champions', introducing peer support workers and developing local policies and protocols to support recovery practice. ABSTRACT: Introduction A study of Irish mental health practitioners (Cleary & Dowling ) identified the need to improve knowledge and attitudes towards recovery. This led to the Advancing Recovery in Ireland Project (ARI) which promoted recovery-orientated services and a need to 'benchmark' progress. There is little evidence regarding the types of educational interventions that maintain positive recovery knowledge and attitudes in providers. Aim The study assessed current knowledge and attitudes to recovery. Methods The methodology of Cleary & Dowling () was replicated. A survey was administered to practitioners (n = 337) using the adapted Recovery Knowledge Inventory (RKI) (Cleary & Dowling ). Results No significant differences were found in recovery scores compared to Cleary & Dowling () or by level of experience. Working in dual settings, being a non-nurse, and training was associated with better recovery scores. Significantly more respondents had received training in recovery (40% versus 23%) compared to Cleary & Dowling (). Training appears to be the strongest factor predicting better recovery knowledge. Conclusions There is considerable scope to improve recovery knowledge. Key recommendations include the need for more recovery training, using 'Recovery Champions', introducing peer support workers and developing local policies and protocols to support recovery working.

OBJECTIVE: There are many uncertainties surrounding the aetiology, treatment and sequelae of hyperemesis gravidarum (HG). Prioritising research questions could reduce research waste, helping researchers and funders direct attention to those questions which most urgently need addressing. The HG priority setting partnership (PSP) was established to identify and rank the top 25 priority research questions important to both patients and clinicians. METHODS: Following the James Lind Alliance (JLA) methodology, an HG PSP steering group was established. Stakeholders representing patients, carers and multidisciplinary professionals completed an online survey to gather uncertainties. Eligible uncertainties related to HG. Uncertainties on nausea and vomiting of pregnancy and those on complementary treatments were not eligible. Questions were verified against the evidence. Two rounds of prioritisation included an online ranking survey and a 1-hour consensus workshop. RESULTS: 1009 participants (938 patients/carers, 118 professionals with overlap between categories) submitted 2899 questions. Questions originated from participants in 26 different countries, and people from 32 countries took part in the first prioritisation stage. 66 unique questions emerged, which were evidence checked according to the agreed protocol. 65 true uncertainties were narrowed via an online ranking survey to 26 unranked uncertainties. The consensus workshop was attended by 19 international patients and clinicians who reached consensus on the top 10 questions for international researchers to address. More patients than professionals took part in the surveys but were equally distributed during the consensus workshop. Participants from low-income and middle-income countries noted that the priorities may be different in their settings. CONCLUSIONS: By following the JLA method, a prioritised list of uncertainties relevant to both HG patients and their clinicians has been identified which can inform the international HG research agenda, funders and policy-makers. While it is possible to conduct an international PSP, results from developed countries may not be as relevant in low-income and middle-income countries.

BackgroundCritical limb ischemia (CLI) is the most severe manifestation of peripheral vascular disease. Revascularization is the preferred therapy, but it is not achievable in 25%–40% of patients due to diffuse anatomic distribution of the disease or medical comorbidities. No-option CLI represents an unmet medical need. Mesenchymal stromal cells (MSCs) may provide salvage therapy through their angiogenic and tissue-trophic properties. This article reports a phase 1b clinical study examining the safety and feasibility of intramuscular transplantation of autologous bone-marrow MSCs for patients with no-option CLI.MethodsTwelve patients were enrolled in the clinical trial, and nine proceeded to bone marrow aspiration and culture expansion of MSCs.ResultsA high rate of karyotype abnormality (>30%) was detected in the produced cell batches, resulting in failure of release for clinical administration. Four patients were treated with the investigational medicinal product (IMP), three with a low dose of 20 × 106 MSCs and one with a mid-dose of 40 × 106 MSCs. There were no serious adverse events related to trial interventions, including bone marrow aspiration, IMP injection or therapy.ConclusionsThe results of this trial conclude that an autologous cell therapy approach with MSCs for critical limb ischemia is limited by the high rate of karyotype abnormalities.

INTRODUCTION: The first case of novel SARS-COV-2 (COVID-19) in Pakistan was detected on 26 February 2020. Pharmacological and non-pharmacological strategies have been tried to lessen the mortality and morbidity burden. Various vaccines have been approved. The Drug Regulatory Authority of Pakistan gave emergency approval for Sinopharm (BBIBP-CorV) COVID-19 vaccine in December 2021. The phase 3 trial of BBIBP-CorV included only 612 participants aged 60 years and above. The primary aim of this study was to assess the safety and efficacy of BBIBPP-CorV (Sinopharm) vaccine within the Pakistani adult population aged 60 or above. The study was carried out in the Faisalabad district of Pakistan. METHODS: A test negative case-control study design was used to assess safety and efficacy of BBIBP-CorV in individuals aged 60 and above against symptomatic infection, hospitalisations and mortality due to SARS-CoV-2 among vaccinated and unvaccinated individuals. ORs were calculated using logistic regression model at 95% CI. ORs were used to calculate the vaccine efficacy (VE) by using the following formula.VE= (1-OR) ×100. RESULTS: 3426 individuals with symptoms of COVID-19 were PCR tested between 5 May 2021 and 31 July 2021. The results showed that Sinopharm vaccine 14 days after the second dose was efficient in reducing the risk of symptomatic COVID-19 infection, hospitalisations and mortality by 94.3%, 60.5% and 98.6%, respectively, among vaccinated individuals with a significant p value of 0.001. CONCLUSION: Our study showed that BBIBP-CorV vaccine is highly effective in preventing infection, hospitalisations and mortality due to COVID-19.

The current demographic shift raises the demand for provision of health care tailored to the complex care needs for older adults. Given the growing number of national care plans and best practice models there is an urgent need to build evidence for inter- and multiprofessional care provision for older people when offered an integrated care approach. The aim of this study was to determine whether an inter-professional or multi-professional care intervention, can improve geriatric patients' health determinants. A systematic review was performed according to PRISMA Guidelines. Databases were searched for clinical trials which compare inter-professional or multi-professional complex care interventions with usual care among people aged ≥60 years, in hospital or emergency care settings. Based on nine studies, inter-professional or multi-professional intervention has no impact on mortality rate but either positive or neutral effects on physical health, psychosocial wellbeing and utilization of health care service. It shows that these inter-professional or multi-professional interventions were feasible. This systematic review highlights the scarcity of evidence showing either positive or neutral impact of intervention based on inter-professional or multi-professional teamwork across care settings on the health determinants among geriatric patients. International harmonization of assessment tools may allow direct comparisons for future interventions.

BACKGROUND: while it is well established that individual patient preferences regarding cardiopulmonary resuscitation (CPR) may change with time, the stability of population preferences, especially during periods of social and economic change, has received little attention. OBJECTIVE: to elicit the resuscitation preferences of older Irish inpatients and to compare the results with an identical study conducted 15 years earlier. METHODS: one hundred and fifty older medical inpatients awaiting discharge in a university teaching hospital or a district general hospital subjects were asked about resuscitation preferences. Results were compared to those elicited from a hundred subjects in 1992. RESULTS: most patients (94%) felt it was a good idea for doctors to discuss CPR routinely with patients, compared with 39% in 1992. In their current health, 6% in 2007 and 76% in 1992 would refuse CPR. The independent predictors of refusal of CPR in current health on logistic regression were age and year of assessment. In the final model, those aged 75-84 years [OR 2.77 (95% CI 1.25-6.13), P = 0.02] and 85 years or more [OR 15.19 (4.26-54.15), P < 0.0001] were more likely than those aged 65-74 years (reference group) to refuse CPR. Those questioned in 2007 [OR 0.04 (0.02-0.81), P < 0.0001] were less likely than those questioned in 1992 (reference group) to refuse CPR. CONCLUSIONS: there has been a significant shift in the attitudes of older Irish inpatients over 15 years towards favouring greater patient participation in decision making and an increased desire for resuscitation.

Venous leg ulcers (VLUs) are the most severe complication caused by the progression of chronic venous insufficiency. They account for approximately 70-90% of all chronic leg ulcers (CLUs). A total of 1% of the Western population will suffer at some time in their lives from a VLU. Furthermore, most CLUs are VLUs, defined as chronic leg wounds that show no tendency to heal after three months of appropriate treatment or are still not fully healed at 12 months. The essential feature of VLUs is their recurrence. VLUs also significantly impact quality of life and could cause social isolation and depression. They also have a significant avoidable economic burden. It is estimated that the treatment of venous ulceration accounts for around 3% of the total expenditure on healthcare. A VLU-free world is a highly desirable aim but could be challenging to achieve with the current knowledge of the pathophysiology and diagnostic and therapeutical protocols. To decrease the incidence of VLUs, the long-term goal must be to identify high-risk patients at an early stage of chronic venous disease and initiate appropriate preventive measures. This review discusses the epidemiology, socioeconomic burden, pathophysiology, diagnosis, modes of conservative and invasive treatment, and prevention of VLUs.