Temporal trends and differences of SARS-CoV-2-specific antibody responses in symptomatic and asymptomatic subjects: a longitudinal study from Umbria in Italy.

OBJECTIVES: Dynamics of antibody responses following SARS-CoV-2 infection are controversial in terms of immunity and persistence. We aimed to assess longitudinally the trend of antibody serological titres, their correlation with clinical severity as well as clinical reinfection during a follow-up. DESIGN: Longitudinal cohort, 12 months follow-up study. SETTING: USL Umbria 2. PARTICIPANTS: Consecutive subjects aged 15-75 who were discharged with the diagnosis of Sars-Cov-2 from the hospitals of the AUSL Umbria 2, or resulted positive to a PCR test for SARS-CoV-2 infection with or without symptoms were recruited. SARS-CoV-2 serological testing for antibodies targeting the Nucleocapside and Spike proteins were determined. RESULTS: Of 184 eligible subjects, 149 were available for evaluation: 17 were classified as oligo/asymptomatic, 107 as symptomatic, 25 as hospital admitted. Participants differed in terms of signs and symptoms as well as treatment. Overall there was a significant difference in terms of antibody titres between groups (anti-S: p<0.00; anti-N: p=0.019). Median anti-S titres in the symptomatic and hospital admitted participants were significantly higher compared with the oligo/asymptomatic participants. During follow-up, the median titre of anti-S antibodies did not show significant variations (p=0.500) and the difference within groups remained constant overtime. Subjects that showed an anti-S titre above the threshold of 12 U/mL were 88.7% at first visit and 88.2% at last follow-up. Anti-N values were higher in the hospital admitted participants compared with the other two groups. Anti-N titre reduced constantly overtime (p<0.001) and across the three groups of participants. The percentage of the subjects with serological titre above threshold (<1.4 U/mL) decreased from 74.5%% to 29.2% (p<0.001). None of the participants developed clinically evident reinfection. CONCLUSION: Anti-N and anti-S correlate well with clinical severity. While anti-N declines overtime, anti-S antibodies persist for at least 1 year.

Ultrasound for diagnosis of birth weight discordance in twin pregnancies.

BACKGROUND: There is a need to standardize monitoring in obstetric research of twin pregnancies. Identification of birth weight discordance (BWD), defined as a difference in the birth weights of twins, is a well-documented phenomenon in twin pregnancies. Ultrasound for the diagnosis of BWD informs complex decision making including whether to intervene medically (via laser photo coagulation) or deliver the twins to avoid fetal morbidities or even death. The question is, how accurate is this measurement? OBJECTIVES: To determine the diagnostic accuracy (sensitivity and specificity) of ultrasound estimated fetal weight discordance (EFWD) of 20% and 25% using different estimated biometric ultrasound measurements compared with the actual BWD as the reference standard in twin pregnancies. SEARCH METHODS: The search for this review was performed on 15 March 2019. We searched CENTRAL, MEDLINE (Ovid), Embase (Ovid), seven other databases, conference proceedings, reference lists and contacted experts. There were no language or date restrictions applied to the electronic searches, and no methodological filters to maximize sensitivity. SELECTION CRITERIA: We selected cohort-type studies with delayed verification that evaluated the accuracy of biometric measurements at ultrasound scanning of twin pregnancies that had been proposed for the diagnosis of estimated BWD, compared to BWD measurements after birth as a reference standard. In addition, we only selected studies that considered twin pregnancies and applied a reference standard for EFWD for the target condition of BWD. DATA COLLECTION AND ANALYSIS: We screened all titles generated by electronic database searches. Two review authors independently assessed the abstracts of all potentially relevant studies. We assessed the identified full papers for eligibility, and extracted data to create 2 × 2 tables. Two review authors independently performed quality assessment using the QUADAS-2 tool. We excluded studies that did not report data in sufficient detail to construct 2 × 2 tables, and where this information was not available from the primary investigators. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included 39 eligible studies with a median study sample size of 140. In terms of risk of bias, there were many unclear statements regarding patient selection, index test and use of proper reference standard. Twenty-one studies (53%) were of methodological concern due to flow and timing. In terms of applicability, most studies were of low concern. Ultrasound for diagnosis of BWD in twin pregnancies at 20% cut-off Twenty-two studies provided data for a BWD of 20% and the summary estimate of sensitivity was 0.51 (95% CI 0.42 to 0.60), and the summary estimate of specificity was 0.91 (95% CI 0.89 to 0.93) (8005 twin pregnancies; very low-certainty evidence). Ultrasound for diagnosis of BWD in twin pregnancies at 25% cut-off Eighteen studies provided data using a BWD discordance of 25%. The summary estimate of sensitivity was 0.46 (95% CI 0.26 to 0.66), and the summary estimate of specificity was 0.93 (95% CI 0.89 to 0.96) (6471 twin pregnancies; very low-certainty evidence). Subgroup analyses were possible for both BWD of 20% and 25%. The diagnostic accuracy did not differ substantially between estimation by abdominal circumference and femur length but femur length had a trend towards higher sensitivity and specificity. Subgroup analyses were not possible by sex of twins, chorionicity or gestational age due to insufficient data. AUTHORS' CONCLUSIONS: Very low-certainty evidence suggests that EFWD identified by ultrasound has low sensitivity but good specificity in detecting BWD in twin pregnancies. There is uncertain diagnostic value of EFWD; this review suggests there is insufficient evidence to support this index as the sole measure for clinical decision making to evaluate the prognosis of twins with growth discordance. The diagnostic accuracy of other measures including amniotic fluid index and umbilical artery Doppler resistive indices in combination with ultrasound for clinical intervention requires evaluation. Future well-designed studies could also evaluate the impact of chorionicity, sex and gestational age in the diagnostic accuracy of ultrasound for EFWD.

Lasers to prevent dental caries: a systematic review.

OBJECTIVE: To assess the effectiveness of lasers (at sub-ablative parameters) in reducing caries incidence compared with traditional prophylactic interventions (TPIs) when used alone or together with other TPIs such as pits and fissures sealant or fluoride gels or varnishes. DESIGN: A systematic review. Data sources include Medline (via PubMed), Embase, Web of Science and the Cochrane Library (December 2019). ELIGIBILITY CRITERIA: Only randomised trials (RCTs) and controlled clinical trials (CCTs) dealing with prophylactic lasers use (vs TPI or untreated teeth) were considered as eligible. We excluded in vitro and ex vivo studies. DATA EXTRACTION: Eligible studies were selected and data extracted independently by two reviewers. Risk of bias was assessed adopting the Cochrane Risk of Bias tool. Data on caries incidence, sealant retention, fluoride uptake, adverse events, treatment duration, patients' discomfort and cost-effectiveness ratio was extracted. DATA ANALYSIS: Extracted data were presented narratively due to the heterogeneity of included studies. RESULTS: Seven RCTs and two CCTs, all with an evident risk of bias, met inclusion criteria, pooling together 269 individuals and 1628 teeth. CO2, neodymium-doped yttrium aluminium garnet, erbium-doped yttrium aluminum garnet (Er:YAG), erbium, chromium: yttrium scandium gallium garnet (Er,Cr:YSGG) and Argon lasers were used. In the permanent dentition, lasers only when used in combination with TPIs were effective in reducing caries when compared with untreated teeth (risk ratio (RR)=0.44 (0.20-0.97); Er:YAG laser) or with TPIs used alone (RR=0.39 (0.22-0.71); CO2 laser). Moreover, Argon laser significantly improved the fluoride uptake into the enamel surfaces (ANalysis Of VAriance (ANOVA) tests: 95%, p<0.0001). Likewise, sealant retention improved when acid etching was performed on previously irradiated enamel fissures by CO2 laser (RR=0.63 (0.38-1.04)) or Er:YAG laser (RR=0.54 (95% CI: 0.34 to 0.87)). In addition, laser resulted safe and well tolerated by patients. CONCLUSION: Despite some positive indications, an inadequate level of evidence was found in the included studies concerning the lasers' effectiveness in preventing caries. Further studies with a higher methodological quality level are required.

Accuracy of ICD-9 codes in identifying patients with peptic ulcer and gastrointestinal hemorrhage in the regional healthcare administrative database of Umbria.

BACKGROUND: Peptic ulcer is a widespread disease, frequently complicated by perforation and bleeding. Administrative databases are useful tool to perform epidemiological and drug utilization studies, but they need a validation process based on a comparison with the original data contained in the medical charts. Our aim was to evaluate the accuracy of the ICD-9 codes in identifying patients with peptic ulcer and gastrointestinal hemorrhage in the regional administrative database of Umbria. METHODS: The index test of our study was the hospital discharge abstract database of the Umbria region (Italy), while the reference standard was the clinical information collected in the medical charts. The study population were adult patients with a hospital discharge for peptic ulcer or gastrointestinal hemorrhage in the period 2012-2014. A random sample of cases and non-cases was selected and the corresponding medical charts were reviewed. Cases of peptic ulcer were confirmed based on endoscopy, radiology, and surgery, while adjudication of gastrointestinal hemorrhage was based on presence of hematemesis, melena, and rectal bleeding. RESULTS: Overall, we reviewed 445 clinical charts of cases and 80 clinical charts of non-cases. The diagnostic accuracy results were: code 531 (gastric ulcer), sensitivity and NPV 98%, specificity 88%, and PPV 91%; code 532 (duodenal ulcer), sensitivity and NPV 100%, specificity and PPV 98%; code 534 (gastrojejunal ulcer), sensitivity and NPV 100%, specificity 70%, and PPV 45%; code 578 (gastrointestinal hemorrhage), sensitivity 96%, specificity 90%, PPV and NPV 94%. CONCLUSIONS: Our results showed a high level of diagnostic accuracy for most of the codes considered. The ICD-9 code 534 of gastrojejunal ulcer had a lower level of specificity and PPV due to false positives, being mainly misclassifications for coding errors. These validated codes can be used for future epidemiological studies and for health services research.

Surgical wound closure by staples or sutures?: Systematic review.

AIM: To compare the effects of sutures and staples for skin closure of surgical wounds. MATERIAL AND METHODS: We included published and unpublished randomized controlled trials (RCTs) and cluster-randomized trials comparing staples with sutures. Patients were adults (aged 18 years or over) who had undergone any type of surgery. The primary outcomes were risk of overall and severe wound infection. Secondary outcomes included length of hospital stay, readmission rate, adverse events, patient satisfaction with cosmetic results, postoperative pain. RESULTS: Forty-two very low to low quality RCTs with a total of 11,067 patients were included. Sutures resulted in slightly fewer overall wound infections (4.90%) compared to staples (6.75%) but it is uncertain whether there is a difference between the groups (risk ratio [RR] 1.20, 95% confidence intervals [CI] 0.80-1.79; patients = 9864; studies = 34; I = 70%). The evidence was also insufficient to state a difference in terms of severe wound infection (staples 1.4% vs sutures 1.3%; RR 1.08, 95% CI 0.61-1.89; patients = 3036; studies = 17; I = 0%), grade of satisfaction (RR 0.99, 95% CI 0.91-1.07; patients = 3243; studies = 14; I = 67%) and hospital stay. Staples may increase the risk of adverse events (7.3% for staples vs 3.5% for sutures; RR 2.00, 95% CI 1.44-2.79; patients = 6246; studies = 21; I = 33%), readmission rate (RR 1.28, 95% CI 0.18-9.05; patients = 2466; studies = 5; I = 66%) and postoperative pain (standardized mean difference [SMD] 0.41,95%CI -0.35 to 1.16; I = 88%, patients = 390 patients, studies = 5). CONCLUSIONS: Due to the lack of high quality evidence, we could not state if sutures are better than staples in terms of wound infection, readmission rate, adverse events, and postoperative pain. With a low quality of evidence, sutures reduce postoperative pain and improve grade of satisfaction with the cosmetic outcome.

Simulated presence therapy for dementia.

BACKGROUND: Dementia is a common and serious neuropsychiatric syndrome, characterised by progressive cognitive and functional decline. The majority of people with dementia develop behavioural disturbances, also known as behavioural and psychological symptoms of dementia (BPSD). Several non-pharmacological interventions have been evaluated to treat BPSD in people with dementia. Simulated presence therapy (SPT), an intervention that uses video or audiotape recordings of family members played to the person with dementia, is a possible approach to treat BPSD. OBJECTIVES: To assess the effects of SPT on behavioural and psychological symptoms and quality of life in people with dementia. SEARCH METHODS: We searched ALOIS (the Specialised Register of the Cochrane Dementia and Cognitive Improvement Group), CENTRAL (The Cochrane Library) (9 April 2020), MEDLINE Ovid SP (1946 to 9 April 2020), Embase Ovid SP (1972 to 9 April 2020), PsycINFO Ovid SP (1806 to 9 April 2020), CINAHL via EBSCOhost (1980 to 9 April 2020), LILACS via BIREME (all dates to 9 April 2020), ClinicalTrials.gov (ClinicalTrials.gov) (all dates to 9 April 2020), and the World Health Organization (WHO) Portal (apps.who.int/trialsearch) (all dates to 9 April 2020). We also checked the reference lists of relevant articles to identify any additional studies. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials, including cross-over studies, that evaluated the efficacy of SPT, consisting of personalised audio or videotape recordings of family members, in people with any form of dementia. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies, assessed risk of bias and extracted data. No meta-analyses were conducted because of substantial heterogeneity among the included studies. MAIN RESULTS: Three trials with 144 participants met the inclusion criteria. Two of the trials had a randomised cross-over design, one was a cross-over trial which we classified as quasi-randomised. Participants in the included studies were people with dementia living in nursing homes. They were predominantly women and had a mean age of over 80 years. SPT was performed using an audio or video recording prepared by family members or surrogates. It varied in its content, frequency of administration and duration. All the studies compared multiple treatments. In one study, SPT was compared with two other interventions; in the other two studies, it was compared with three other interventions. Specifically, SPT was compared to usual care, personalised music (two studies), a 'placebo' audiotape containing the voice of a person (two studies), and one-to-one social interaction performed by trained research assistants (one study). In terms of outcomes evaluated, one study considered agitation and withdrawn behaviour (both assessed with three methods); the second study evaluated verbal disruptive behaviour (assessed with three methods); and the third study evaluated physically agitated behaviour and verbally agitated behaviour (the method used was not clearly described). According to the GRADE criteria, the overall quality of the evidence was very low due to very small numbers of participants and risk of bias in the included studies; (none of the trials was at low risk of selection bias; all the trials were at high risk of performance bias; one trial was at high risk of attrition bias; and all had unclear selective reporting). Because of variation in the participants, the format of SPT, the comparison interventions, and the measures used to assess outcomes, we judged the results unsuitable for a meta-analysis. Within each trial, the effect of SPT on behaviour, compared to usual care, was mixed and depended on the measure used. Two trials which included a personalised music intervention reported no significant differences between simulated presence and music on behavioural outcomes. Because the overall quality of the evidence was very low, we were very uncertain regarding all the results None of the studies evaluated quality of life or any of our secondary outcome measures (performance of activities of daily living, dropout and carer burden). AUTHORS' CONCLUSIONS: We were unable to draw any conclusions about the efficacy of SPT for treating behavioural and psychological symptoms and improving quality of life of people with dementia. New high-quality studies are needed to investigate the effect of SPT.

Non-pharmacological, non-surgical interventions for urinary incontinence in older persons: A systematic review of systematic reviews. The SENATOR project ONTOP series.

BACKGROUND: Urinary incontinence is especially common in older age. Non-pharmacological therapies are particularly desirable in this group. OBJECTIVE: To define optimal evidence-based non-pharmacological, non-surgical therapies for urinary incontinence in older persons. METHODS: A Delphi process determined critical outcome measures of interest. Studies of any non-pharmacological intervention reporting critical outcomes were identified through database searches for relevant systematic reviews in Medline, Embase, CINAHL, PsycInfo and Cochrane up to June 2018. Primary trials with a population mean age ≥65years were identified, from which data were extracted and risk of bias was assessed. Qualitative analysis and meta-analysis, when possible, were undertaken, followed by grading of the evidence using GradePro software. Finally, bullet-point recommendations were formulated for the indications and contraindications for non-pharmacological interventions for urinary incontinence in older persons. RESULTS: Frequency of incontinence was identified as a critically important outcome. In total, 33 systematic reviews were identified with 27 primary trials meeting inclusion criteria. Evaluated therapies included exercise therapy, habit retraining, behavioural therapy, electrical stimulation, transcutaneous tibial nerve stimulation, magnetic stimulation, caffeine reduction and acupuncture. From meta-analysis, group exercise therapy and behavioural therapy in women were beneficial in reducing episodes of incontinence (mean reduction of 1.07 (95 %CI 0.69-1.45) and 0.74 (95 %CI 0.42-1.06) episodes per day respectively, evidence grade 'moderate'). Evidence for other interventions was limited and of insufficient quality. CONCLUSIONS: There is sufficient evidence to warrant recommendation of group exercise therapy for stress incontinence and behavioural therapy for urgency, stress or mixed urinary incontinence in older women. Evidence was insufficient to recommend any other non-drug therapy.

Validity of cerebrovascular ICD-9-CM codes in healthcare administrative databases. The Umbria Data-Value Project.

BACKGROUND: Validation of administrative databases for cerebrovascular diseases is crucial for epidemiological, outcome, and health services research. The aim of this study was to validate ICD-9 codes for hemorrhagic or ischemic stroke in administrative databases, to use them for a comprehensive assessment of the burden of disease in terms of major outcomes, such as mortality, hospital readmissions, and use of healthcare resources. METHODS: We considered the hospital discharge abstract database of the Umbria Region (890,000 residents). Source population was represented by patients aged >18 discharged from hospital with a diagnosis of hemorrhagic or ischemic stroke between 2012 and 2014 using ICD-9-CM codes in primary position. We randomly selected and reviewed medical charts of cases and non-cases from hospitals. For case ascertainment we considered symptoms and instrumental tests reported in the medical charts. Diagnostic accuracy measures were computed using 2x2 tables. RESULTS: We reviewed 767 medical charts for cases and 78 charts for non-cases. Diagnostic accuracy measures were: subarachnoid hemorrhage: sensitivity (SE) 100% (95% CI: 97%-100%), specificity (SP) 96% (90-99), positive predictive value (PPV) 98% (93-100), negative predictive value (NPV) 100% (95-100); intracerebral hemorrhage: SE 100% (97-100), SP 98% (91-100), PPV 98% (94-100), NPV 100% (95-100); other and unspecified intracranial hemorrhage: SE 100% (97-100), SP 96% (90-99), PPV 98% (93-100), NPV 100% (95-100); ischemic stroke due to occlusion and stenosis of precerebral arteries: SE 99% (94-100), SP 66 (57-75), PPV 70% (61-77), NPV 99% (93-100); occlusion of cerebral arteries: SE 100% (97-100), SP 87% (78-93), PPV 91% (84-95), NPV 100% (95-100); acute, but ill-defined, cerebrovascular disease: SE 100% (97-100), SP 78% (69-86), PPV % 83 (75-89), NPV 100% (95-100). CONCLUSIONS: Case ascertainment for both ischemic and hemorrhagic stroke showed good or high levels of accuracy within the regional healthcare databases in Umbria. This database can confidently be employed for epidemiological, outcome, and health services research related to any type of stroke.

[Epidemiology of postpartum hemorrhages in the Umbrian population in the years 2006-2017.] / Epidemiologia delle emorragie post partum nella popolazione umbra nel periodo 2006-2017.

INTRODUCTION: Postpartum haemorrhage (PPH) is one of the main causes of mortality and severe maternal morbidity and its incidence is increasing also in Western countries. Aim of this study is to estimate the incidence and the trend of PPH in the Umbrian population using the validated Umbrian health database and to identify possible determinants for the development of PPH. METHODS: The source of the data was the regional Healthcare Database of the Umbria Region. The population of interest was represented by women who gave birth in Umbria between 2006 and 2017. The PPH was identified from the hospital data using the ICD-9-CM 666.x codes. Demographic data, principal and secondary diagnoses and data on maternal morbidity and blood component transfusion were collected. The incidence of PPH was calculated taking into account cases of PPH over the total number of births. The determinants of PPH, the associated morbidity and the variation in the severity of the PPH over time have been identified by logistic regression models. RESULTS: In Umbria, between 2006 and 2017, 93,403 births were registered (69% by vaginal delivery and 31% by caesarean section) and the rate of caesarean sections decreased by about 4%. The incidence of PPH increased three-fold during this period with an increase (p<0.001) of women with PPH who received transfusions. Regarding the caesarean sections, the PPH trend increased by 53% (p=0.3), while in the vaginal deliveries the PPHs increased by 233% (p<0.001). Logistic regression analysis showed that possible risk factors for the occurrence of PPH are maternal morbidity (OR 22.8, 95% CI 18.5-30.0), twin birth (OR 2.0, 95% CI 1.3-3.2) and antepartum haemorrhage (OR 5.7, 95% CI 3.1-10.4). CONCLUSIONS: The incidence of PPH has increased in recent years, while the morbidity associated with PPH has remained substantially unchanged. The study identified several risk factors responsible for PPH that can be used in the monitoring of pregnant women and for planning prevention strategies such as Patient Blood Management.

[Postpartum haemorrhage in Umbria: accuracy of the regional health information system for the code ICD-9-CM 666.x.] / Emorragia post partum in Umbria: accuratezza del sistema informativo sanitario regionale per il codice ICD-9-CM 666.x.

INTRODUCTION: Postpartum haemorrhage (PPH) is the main cause of morbidity and mortality for pregnant women. Administrative databases are useful sources of information for the assessment of PPH and related outcomes, once the corresponding ICD-9-CM code is validated. The objective of the present study is to evaluate the accuracy of the ICD-9-CM code related to PPH. MATERIAL AND METHODS: Source of the data was the Regional Healthcare Database of the Umbria Region. The population of interest were women with at least 20 weeks of gestation that delivered in any hospital in the Umbria Region during 2012-2016. Cases of interest were identified using the ICD-9-CM 666.x code. For validation purposes, both cases (women who delivered and developed PPH) and non-cases (women who delivered without occurrence of PPH) were considered and algorithms proposed. The basic criterion used for the validity of ICD-9-CM codes was the presence of bleeding ≥500 ml. Additional criteria based on values of haemoglobin or transfusion of red blood cells were considered. Sensitivity, specificity and predictive values were calculated. RESULTS: Medical charts of 422 cases and 200 non-cases were examined. Accuracy results for code 666.x related to the presence of bleeding ≥500 ml were: sensitivity 97% (95% CI, 96-99%), specificity 70% (65-76%), positive predictive value (PPV) 79% (76-82%) and negative predictive value (NPV) 95% (91-97%). The best algorithm was the one that, in addition to the basic criterion, considered both the haemoglobin values and red blood cell transfusion: sensitivity 93% (90-95%), specificity 85% (80-90%), PPV 92% (89-94%) and NPV 86% (81-90%). ICD-9 subcodes showed a higher specificity and PPV for immediate bleeding (666.0, 666.1) than delayed or secondary haemorrhage (666.2). CONCLUSIONS: The accuracy data from the present study confirm that the Regional Healthcare Database of the Umbria Region can be used as a reliable source for the evaluation of epidemiological studies relating to PPHs, in order to improve the quality of maternity care.

A diagnostic accuracy study validating cardiovascular ICD-9-CM codes in healthcare administrative databases. The Umbria Data-Value Project.

BACKGROUND: Administrative healthcare databases are useful and inexpensive tools that can provide a comprehensive assessment of the burden of diseases in terms of major outcomes, such as mortality, hospital readmissions, and use of healthcare resources. However, a crucial issue is the reliability of information gathered. The aim of this study was to validate ICD-9 codes for several major cardiovascular conditions, i.e., acute myocardial infarction (AMI), atrial fibrillation/flutter (AF), and heart failure (HF), in order to use them for epidemiological, outcome, and health services research. METHODS: Data from the centralised administrative database of the Umbria Region (890,000 residents, located in Central Italy) were considered. Patients with a first hospital discharge for AMI, AF/flutter, and HF, between 2012 and 2014, were identified using ICD-9-CM codes in primary position. A sample of cases and non-cases was randomly selected, and the corresponding medical charts reviewed by specifically trained investigators. For each disease, case ascertainment was based on all clinical, laboratory, and instrumental examinations available in medical charts. Sensitivity, specificity, and predictive values with 95% confidence intervals (CIs), were calculated. RESULTS: We reviewed 458 medical charts, 128 for AMI, 127 for AF/flutter, 127 for HF, and 76 of non-cases for each condition. Diagnostic accuracy measures of the original discharge diagnosis were as follows. AMI: sensitivity 98% (95% CI, 94-100%), specificity 91% (95% CI, 83-97%), positive predictive value (PPV) 95% (95% CI, 89-98%), negative predictive value (NPV) 97% (95% CI, 91-100%). AF/flutter: sensitivity 95% (95% CI, 90-98%), specificity 95% (95% CI, 87-99%), PPV 97% (95% CI, 92-99%), NPV 92% (95% CI, 84-97%). HF: sensitivity 96% (95% CI, 91-99%), specificity 90% (95% CI, 81-96%), PPV 94% (95% CI, 88-97%), NPV 93% (95% CI, 85-98%). CONCLUSION: The case ascertainment for AMI, AF and flutter, and HF, showed a high level of accuracy (≥ 90%). The healthcare administrative database of the Umbria Region can be confidently used for epidemiological, outcome, and health services research.

Nonpharmacologic Management of Orthostatic Hypotension in Older People: A Systematic Review. The SENATOR ONTOP Series.

OBJECTIVES: Nonpharmacologic therapies are often recommended as a first-line treatment for orthostatic hypotension (OH). However, the true effect of nonpharmacologic therapy remains unclear, particularly in the older population. We undertook a systematic review evaluating the efficacy of nonpharmacologic interventions in older people with OH to provide evidence-based recommendations. DESIGN: Systematic review of systematic reviews. SETTING AND PARTICIPANTS: MEDLINE, PubMed, EMBASE, and Cochrane Database of Systematic Reviews, CINHAL, and PsycINFO were searched up to June 2018. Two reviewers identified eligible systematic reviews from which primary studies were selected. We included both randomized and nonrandomized studies that evaluated any type of nonpharmacologic intervention and reported outcomes of change in postural drop in systolic blood pressure (SBP) and/or orthostatic symptoms measured using any validated instrument. The Cochrane risk of bias tool was used, with recommendations based on the GRADE approach. RESULTS: Eleven trials were included. Meta-analysis of lower limb compression showed a reduction in the postural drop in SBP of 9.83 mmHg [95% confidence interval (CI) -12.56, -7.11], whereas abdominal compression showed a larger reduction in postural drop in SBP of 12.30 mmHg (95% CI -18.20, -6.39). Compression therapy was also beneficial in reducing OH symptoms. However, the quality of the evidence for compression therapy was very poor. One study each was identified for sleeping with head-up (SHU), home-based resistance training (HBRT), and multicomponent intervention but did not significantly reduce postural SBP drop. Bolus water drinking was effective in 1 study but the study was of low quality. CONCLUSIONS/IMPLICATIONS: There is no high-quality evidence to recommend any of the nonpharmacologic therapies for the management of OH in older people. Yet, we make a weak recommendation for lower limb and abdominal compression therapy based on very low quality evidence. Large-scale trials are warranted in older people to substantiate the efficacy of nonpharmacologic therapies in OH.

Oral iron-based interventions for prevention of critical outcomes in pregnancy and postnatal care: An overview and update of systematic reviews.

OBJECTIVE: The aim of this work was to summarize and update the evidence concerning oral iron-based interventions compared to placebo or no iron-based interventions to prevent critical outcomes in pregnancy or treat critical outcomes in the postpartum phase. METHOD: Published systematic reviews (Feb 2018) and primary studies (from 2015 to March 2018) retrieved from MEDLINE, EMBASE, and the Cochrane Library were examined. The AMSTAR (Assessing the Methodological Quality of Systematic Reviews) tool was used to assess the quality of reviews. GRADE was used to rate the quality of the evidence for critical outcomes. RESULTS: Antenatal care: Compared to placebo/no treatment, iron-based therapies reduced maternal anemia at term by 59% (seven trials at low risk of bias, RR 0.41, 95% CI 0.23-0.73; I2  = 86%; moderate-quality evidence) and maternal iron deficiency anemia by 67% (RR 0.33, 95% CI 0.16-0.69; I2  = 49%). There was no evidence of difference between iron-based therapies vs control in terms of side effects (RR 1.42, 95% CI 0.91-2.21), preterm delivery (13 studies: RR 0.93, 95% CI 0.84-1.03; low-quality evidence), low birthweight (RR 0.94, 95% CI 0.79-1.13; low-quality evidence) and infant mortality (RR 0.93, 0.72-1.20; low-quality evidence). POSTNATAL CARE: There was insufficient evidence to determine whether iron-based therapies can reduce postpartum anemia. CONCLUSION: Iron supplementation is effective in preventing maternal anemia at term but not low birthweight, preterm delivery or infant mortality.

Incidence and prevalence of Parkinson's disease in the Italian region of Umbria: a population-based study using healthcare administrative databases.

Parkinson's disease is known to pose a significant burden on society in industrialized countries. However, few studies have been conducted in Italy using administrative healthcare databases for epidemiological purposes. We wanted to estimate the incidence and prevalence rates of Parkinson's disease in the Italian region of Umbria by means of linkage between several sources of administrative healthcare data: hospitalization episodes, exemptions from medical charges, drug prescriptions from general practitioners and physicians working in the public sector. Using a pre-defined algorithm, we estimated incident and prevalent cases of Parkinson's disease for the year 2016. The regional incidence rate, adjusted with Italian standard population data, was 0.40 new cases/1000 person-years (0.41 in females, 0.39 in males). We estimated that 5550 subjects were affected by Parkinson's disease, leading to an age-adjusted prevalence rate of 5.42/1000 inhabitants. Prevalence and incidence increased with age and male gender. However, due to the longer life expectancy of females, the absolute number of prevalent cases was greater among females. The heterogeneity of spatial distribution of disease was high. A considerable proportion of prevalent cases was hospitalized in 2016. The most recurrent reasons for hospitalization episodes were disorders related to the nervous system, respiratory system, cardiovascular system, and musculoskeletal and connective tissue apparatus. The study findings support the feasibility of future epidemiological studies of Parkinson's disease with administrative data as well as the need for an integrative care pathway for the patients with Parkinson's disease.

Intraoperative neuromonitoring versus visual nerve identification for prevention of recurrent laryngeal nerve injury in adults undergoing thyroid surgery.

BACKGROUND: Injuries to the recurrent inferior laryngeal nerve (RILN) remain one of the major post-operative complications after thyroid and parathyroid surgery. Damage to this nerve can result in a temporary or permanent palsy, which is associated with vocal cord paresis or paralysis. Visual identification of the RILN is a common procedure to prevent nerve injury during thyroid and parathyroid surgery. Recently, intraoperative neuromonitoring (IONM) has been introduced in order to facilitate the localisation of the nerves and to prevent their injury during surgery. IONM permits nerve identification using an electrode, where, in order to measure the nerve response, the electric field is converted to an acoustic signal. OBJECTIVES: To assess the effects of IONM versus visual nerve identification for the prevention of RILN injury in adults undergoing thyroid surgery. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, ICTRP Search Portal and ClinicalTrials.gov. The date of the last search of all databases was 21 August 2018. We did not apply any language restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing IONM nerve identification plus visual nerve identification versus visual nerve identification alone for prevention of RILN injury in adults undergoing thyroid surgery DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts for relevance. One review author carried out screening for inclusion, data extraction and 'Risk of bias' assessment and a second review author checked them. For dichotomous outcomes, we calculated risk ratios (RRs) with 95% confidence intervals (CIs). For continuous outcomes, we calculated mean differences (MDs) with 95% CIs. We assessed trials for certainty of the evidence using the GRADE instrument. MAIN RESULTS: Five RCTs with 1558 participants (781 participants were randomly assigned to IONM and 777 to visual nerve identification only) met the inclusion criteria; two trials were performed in Poland and one trial each was performed in China, Korea and Turkey. Inclusion and exclusion criteria differed among trials: previous thyroid or parathyroid surgery was an exclusion criterion in three trials. In contrast, this was a specific inclusion criterion in another trial. Three trials had central neck compartment dissection or lateral neck dissection and Graves' disease as exclusion criteria. The mean duration of follow-up ranged from 6 to 12 months. The mean age of participants ranged between 41.7 years and 51.9 years.There was no firm evidence of an advantage or disadvantage comparing IONM with visual nerve identification only for permanent RILN palsy (RR 0.77, 95% CI 0.33 to 1.77; P = 0.54; 4 trials; 2895 nerves at risk; very low-certainty evidence) or transient RILN palsy (RR 0.62, 95% CI 0.35 to 1.08; P = 0.09; 4 trials; 2895 nerves at risk; very low-certainty evidence). None of the trials reported health-related quality of life. Transient hypoparathyroidism as an adverse event was not substantially different between intervention and comparator groups (RR 1.25; 95% CI 0.45 to 3.47; P = 0.66; 2 trials; 286 participants; very low-certainty evidence). Operative time was comparable between IONM and visual nerve monitoring alone (MD 5.5 minutes, 95% CI -0.7 to 11.8; P = 0.08; 3 trials; 1251 participants; very low-certainty evidence). Three of five included trials provided data on all-cause mortality: no deaths were reported. None of the trials reported socioeconomic effects. The evidence reported in this review was mostly of very low certainty, particularly because of risk of bias, a high degree of imprecision due to wide confidence intervals and substantial between-study heterogeneity. AUTHORS' CONCLUSIONS: Results from this systematic review and meta-analysis indicate that there is currently no conclusive evidence for the superiority or inferiority of IONM over visual nerve identification only on any of the outcomes measured. Well-designed, executed, analysed and reported RCTs with a larger number of participants and longer follow-up, employing the latest IONM technology and applying new surgical techniques are needed.

Non-pharmacological interventions for the improvement of post-stroke quality of life amongst older stroke survivors: a systematic review of systematic reviews (The SENATOR ONTOP series).

PURPOSE: The efficacy of non-pharmacological stroke rehabilitation approaches for older stroke survivors is largely unknown, particularly in relation to psychosocial outcomes such as quality of life. This systematic review examined the evidence for such interventions as part of the Optimal Evidence-Based Non-Drug Therapies in Older Persons (ONTOP) project conducted under an European Union funded project called the Software Engine for the Assessment and Optimisation of Drug and Non-Drug Therapies in Older Persons (SENATOR) [ http://www.senator-project.eu ]. METHODS: Thirteen experts in geriatric medicine, as part of a Delphi panel, agreed quality of life to be a critical outcome of stroke rehabilitation. A comprehensive search strategy was developed and databases were searched for eligible systematic reviews from which trials meeting our criteria were identified. Eligible papers were then double reviewed. Due to heterogeneity, narrative analysis was performed. Cochrane risk of bias and GRADE assessment tools were used to assess bias and quality of evidence. RESULTS: We identified 28 trials, spanning ten types of intervention. Limited evidence supports the use of additional occupational therapy and physiotherapy, with very limited evidence supporting our recommendation to explore caregiver training, constraint-induced movement therapy, device-assisted physiotherapy, and self-management education further. CONCLUSION: Limited evidence suggests a range of non-pharmacological interventions may improve the quality of life of older stroke survivors. However, evidence is limited by low study quality and the small number of studies targeting older stroke survivors. We recommend future studies explore such interventions exclusively in older adult populations and improve methodological and outcome reporting.

Diagnostic, preventive and therapeutic evidence in obstetrics for the implementation of patient blood management: a systematic review protocol.

INTRODUCTION: Patientblood management (PBM) is defined as the application of evidence-based diagnostic, preventive and therapeutic approaches designed to maintain haemoglobin concentration, optimise haemostasis and minimise blood loss in an effort to improve patient outcome. We propose a protocol for the assessment of the evidence of diagnostic, preventive and therapeutic approaches for the management of relevant outcomes in obstetrics with the aim to create a framework for PBM implementation. METHODS AND ANALYSIS: Diagnostic, preventive and therapeutic tools will be considered in the gynaecological conditions and obstetrics setting (antenatal care, peripartum care and maternity care). For each condition, (1) clinical questions based on prioritised outcomes will be developed; (2) evidence will be retrieved systematically from electronic medical literature (MEDLINE, EMBASE, the Cochrane Library, Web of Science, and CINAHL); (3) quality of the reviews will be assessed using the AMSTAR (A Measurement Tool to Assess Systematic Reviews) checklist; quality of primary intervention studies will be assessed using the risk of bias tool (Cochrane method); quality of diagnostic primary studies will be assessed using QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies); (4) the Grading of Recommendations Assessment, Development and Evaluation method will be applied to rate the quality of the evidence and to develop recommendations. ETHICS AND DISSEMINATION: For each diagnostic, preventive or therapeutic intervention evaluated, a manuscript comprising the evidence retrieved and the recommendation produced will be provided and published in peer-reviewed journals. Ethical approval is not required.

Preoperative radiotherapy and curative surgery for the management of localised rectal carcinoma.

BACKGROUND: This is an update of the original review published in 2007.Carcinoma of the rectum is a common malignancy, especially in high income countries. Local recurrence may occur after surgery alone. Preoperative radiotherapy (PRT) has the potential to reduce the risk of local recurrence and improve outcomes in rectal cancer. OBJECTIVES: To determine the effect of preoperative radiotherapy for people with localised resectable rectal cancer compared to surgery alone. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library; Issue 5, 2018) (4 June 2018), MEDLINE (Ovid) (1950 to 4 June 2018), and Embase (Ovid) (1974 to 4 June 2018). We also searched ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) for relevant ongoing trials (4 June 2018). SELECTION CRITERIA: We included randomised controlled trials comparing PRT and surgery with surgery alone for people with localised advanced rectal cancer planned for radical surgery. We excluded trials that did not use contemporary radiotherapy techniques (with more than two fields to the pelvis). DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the 'Risk of bias' domains for each included trial, and extracted data. For time-to-event data, we calculated the Peto odds ratio (Peto OR) and variances, and for dichotomous data we calculated risk ratios (RR) using the random-effects method. Potential sources of heterogeneity hypothesised a priori included study quality, staging, and the use of total mesorectal excision (TME) surgery. MAIN RESULTS: We included four trials with a total of 4663 participants. All four trials reported short PRT courses, with three trials using 25 Gy in five fractions, and one trial using 20 Gy in four fractions. Only one study specifically required TME surgery for inclusion, whereas in another study 90% of participants received TME surgery.Preoperative radiotherapy probably reduces overall mortality at 4 to 12 years' follow-up (4 trials, 4663 participants; Peto OR 0.90, 95% CI 0.83 to 0.98; moderate-quality evidence). For every 1000 people who undergo surgery alone, 454 would die compared with 45 fewer (the true effect may lie between 77 fewer to 9 fewer) in the PRT group. There was some evidence from subgroup analyses that in trials using TME no or little effect of PRT on survival (P = 0.03 for the difference between subgroups).Preoperative radiotherapy may have little or no effect in reducing cause-specific mortality for rectal cancer (2 trials, 2145 participants; Peto OR 0.89, 95% CI 0.77 to 1.03; low-quality evidence).We found moderate-quality evidence that PRT reduces local recurrence (4 trials, 4663 participants; Peto OR 0.48, 95% CI 0.40 to 0.57). In absolute terms, 161 out of 1000 patients receiving surgery alone would experience local recurrence compared with 83 fewer with PRT. The results were consistent in TME and non-TME studies.There may be little or no difference in curative resection (4 trials, 4673 participants; RR 1.00, 95% CI 0.97 to 1.02; low-quality evidence) or in the need for sphincter-sparing surgery (3 trials, 4379 participants; RR 0.99, 95% CI 0.94 to 1.04; I2 = 0%; low-quality evidence) between PRT and surgery alone.Low-quality evidence suggests that PRT may increase the risk of sepsis from 13% to 16% (2 trials, 2698 participants; RR 1.25, 95% CI 1.04 to 1.52) and surgical complications from 25% to 30% (2 trials, 2698 participants; RR 1.20, 95% CI 1.01 to 1.42) compared to surgery alone.Two trials evaluated quality of life using different scales. Both studies concluded that sexual dysfunction occurred more in the PRT group. Mixed results were found for faecal incontinence, and irradiated participants tended to resume work later than non-irradiated participants between 6 and 12 months, but this effect had attenuated after 18 months (low-quality evidence). AUTHORS' CONCLUSIONS: We found moderate-quality evidence that PRT reduces overall mortality. Subgroup analysis did not confirm this effect in people undergoing TME surgery. We found consistent evidence that PRT reduces local recurrence. Risk of sepsis and postsurgical complications may be higher with PRT.The main limitation of the findings of the present review concerns their applicability. The included trials only assessed short-course radiotherapy and did not use chemotherapy, which is widely used in the contemporary management of rectal cancer disease. The differences between the trials regarding the criteria used to define rectal cancer, staging, radiotherapy delivered, the time between radiotherapy and surgery, and the use of adjuvant or postoperative therapy did not appear to influence the size of effect across the studies.Future trials should focus on identifying participants that are most likely to benefit from PRT especially in terms of improving local control, sphincter preservation, and overall survival while reducing acute and late toxicities (especially rectal and sexual function), as well as determining the effect of radiotherapy when chemotherapy is used and the optimal timing of surgery following radiotherapy.

Non-pharmacological interventions for the improvement of post-stroke activities of daily living and disability amongst older stroke survivors: A systematic review.

Globally, stroke remains a leading cause of death and disability, with older adults disproportionately affected. Numerous non-pharmacological stroke rehabilitation approaches are in use to address impairments, but their efficacy in older persons is largely unknown. This systematic review examined the evidence for such interventions as part of the Optimal Evidence-Based Non-Drug Therapies in Older Persons (ONTOP) project conducted under an European Union funded project called the Software Engine for the Assessment and Optimisation of Drug and Non-Drug Therapies in Older Persons (SENATOR) [http://www.senator-project.eu]. A Delphi panel of European geriatric experts agreed activities of daily living and disability to be of critical importance as stroke rehabilitation outcomes. A comprehensive search strategy was developed and five databases (Pubmed, CINAHL, Embase, PsycInfo and Cochrane Database of Systematic Reviews) searched for eligible systematic reviews. Primary studies meeting our criteria (non-pharmacologic interventions, involving stroke survivors aged ≥65 years, assessing activities of daily living and/or disability as outcome) were then identified from these reviews. Eligible papers were double reviewed, and due to heterogeneity, narrative analysis performed. Cochrane risk of bias and GRADE assessment tools were used to assess bias and quality of evidence, allowing us to make recommendations regarding specific non-pharmacologic rehabilitation in older stroke survivors. In total, 72 primary articles were reviewed spanning 14 types of non-pharmacological intervention. Non-pharmacological interventions based on physiotherapy and occupational therapy techniques improved activities of daily living amongst older stroke survivors. However, no evidence was found to support use of any non-pharmacological approach to benefit older stroke survivors' disability. Evidence was limited by poor study quality and the small number of studies targeting older stroke survivors. We recommend future studies explore such interventions exclusively in older adult populations and improve methodological and outcome reporting.