bluuebunny/crossref_metadata_2025 huggingface dataset:
The combination of a neprilysin inhibitor (sacubitril) and angiotensin-II receptor blocker (valsartan) improves ejection fraction and longitudinal strain in mice treated with doxorubicin through NLRP3
Authors: Quagliariello V , Bonelli A , Paccone A , Buccolo S , Iovine M , Rea D , Cerrone F , Botti G , Maurea N
Published: October 2021

Background

Doxorubicin-mediated- adverse cardiovascular events are among the leading causes of morbidity and mortality in breast cancer patients. Sacubitril-valsartan (LCZ 696) is a combination drug, made up of neprilysin inhibitor sacubitril and angiotensin II receptor blocker valsartan, used for the treatment of heart failure in patients with a reduced ejection fraction.

Purpose

Here, we aim to assess whether LCZ 696, administered during doxorubicin, reduces in vitro anticancer drugs-related cardiotoxicity compared to Valsartan (V), used as a control drug.

Methods

Human fetal cardiomyocytes (HFC cell line) were exposed to subclinical concentration of doxorubicin (at 200 nM) alone or in combination with LCZ-696 (100 mM) for 72 h. After the incubation period, we performed the following tests: determination of cell viability, through analysis of mitochondrial dehydrogenase activity, study of lipid peroxidation (quantifying cellular Malondialdehyde and 4-hydroxynonenal), intracellular Ca2+ homeostasis. Moreover, pro-inflammatory studied were also performed (activation of NLRP3 inflammasome; expression of TLR4/MyD88; mTORC1 Fox01/3a; transcriptional activation of p65/NF-κB and secretion of cytokines involved in cardiotoxicity (Interleukins 1β, 8, 6). C57Bl/6 mice were untreated (Sham, n=6) or treated for 10 days with doxorubicin (DOXO, n=6), LCZ-696 (LCZ, n=6) or doxorubicin combined to LCZ-696 (DOXO-LCZ, n=6). DOXO was injected intraperitoneally. Ejection fraction, radial and longitudinal strain were analyzed through transthoracic echocardiography (Vevo 2100). Cardiac tissue expression of NLRP3 inflammasome, Myd8, NF-kB and chemokines and cytokines were quantified after treatments through ELISA method.

Results

LCZ 696 co-incubated with doxorubicin exerts cardioprotective effects, enhancing cell viability of 48–54.6% compared to only doxorubicin-treated cells (p<0,001 for all); LCZ 696 reduced significantly the cardiotoxicity through MyD88/NF-KB/cytokines axis and mTORC1 Fox01/3α mediated mechanisms. In preclinical study, LCZ 696 improved significantly the EF and prevented the reduction of radial and longitudinal strain after 10 days of treatment with doxorubicin. A reduced expression of pro-inflammatory cytokines, NLRP3, MyD88 and NF-kB in heart tissues was also seen in DOXO-LCZ group compared to DOXO mice (p<0.001)

Conclusion

We demonstrated, for the first time, that the LCZ696 exerts direct effects in cardiomyocytes and preclinical models during doxorubicin exposure, turning on a new light on its possible use in cancer patients to reduce cardiovascular side effects.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Ministero della Salute, Ricerca Corrente project
Irreversible cardiac remodeling promotes cancer progression via secreted factors in ATF3 transgenic mouse model
Authors: Awwad L , Aronheim A
Published: October 2021

Cardiac hypertrophy and cancer are the leading cause of deaths worldwide. While heart failure and cancer have been considered separate diseases, it is becoming evident that they are highly connected and affect each other's outcome. Recent studies using mouse models mimicking myocardial infraction and aortic stenosis were shown to promote cancer progression. These two mouse models involve major irreversible surgeries. Here, we employed a transgenic mouse model for heart hypertrophy and examined the crosstalk between the hypertrophied heart and cancer progression. Heart hypertrophy was induced by adult ATF3 expression in cardiomyocytes followed by either PyMT, breast cancer cells or Lewis lung carcinoma (LLC) cells implantation. PyMT and LLC tumors grow larger in size and display increased cell proliferation in ATF3-transgenic mice as compared with control mice. In addition, pulmonary experimental metastasis assay revealed augmented number and size of metastasis lesions in the lungs. Subsequently, we identified five putative cardiac secreted factors that are highly expressed in the hearts derived from ATF3-transgenic that may be involved in tumor progression. These include Fibronectin, CP, serpin3, CTgF and PSTN. Next, we addressed whether the cause or the effect are necessary to promote tumor growth. Towards this end, ATF3 expression was turned-off after cardiac hypertrophy development followed by cancer cell implantation. The tumor promotion phenotype as well as enhancement of metastatic seeding in these mice was fully preserved, suggesting the generation of an irreversible viscous cycle that lead to cancer progression. Significantly, the expression of Fibronectin and CTgF was dampened in the presence of doxycycline, thus exclude their putative role in mediating the tumor promotion and metastatic seeding phenotypes.

Collectively, heart hypertrophy and cancer diseases communicate via secreted factors that result in cancer promotion and disease deterioration.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Israel Science Foundation
Breast cancer radiotherapy and risk of pacemaker implantation: an epidemiologic analysis using the French nationwide claims database
Authors: Errahmani M Y , Thariat J , Ferrieres J , Bernier M O , Boveda S , Jacob S
Published: October 2021

Background

Radiotherapy (RT) is a major treatment for breast cancer (BC), but it is also associated with an increased long-term (>5–10 years) risk of cardiac complications. Specific data on cardiac arrhythmias and conduction disorders are warranted.

Purpose

To evaluate whether pacemaker (PM) implantation risk is higher in BC patients treated with RT compared to the general population or population of BC patients treated without RT.

Methods

Our study was based on the Echantillon Généraliste de Bénéficiaires (EGB), the 1/97 random sample of the French nationwide health insurance claims database. The population of patients treated for BC consisted of adult women with a first BC identified by the ICD-10 diagnosis codes between 2008 and 2016, and followed through 2018. PM implantations and RT were identified with medical procedures codes in the french Common Classification of Medical Procedures (CCAM). For each year from 2008 to 2018, the reference population included all adult women of the EGB database. History of PM or BC was an exclusion criteria. Annual incidence rates of PM implantations were evaluated between 2008 and 2018 in the reference populations. The number of PM cases observed in BC patients at least one year after BC diagnosis was compared with the expected number of PM cases calculated by using reference incidence rates with age standardization. We then computed the standardized incidence ratio (SIR) as the ratio of the observed number of PM to the expected number of PM, with 95% confidence intervals (CIs). Thereafter, a survival analysis was performed in BC patients using a Cox regression model (Hazard Ratio – HR) in order to evaluate the risk of PM associated with treatment including RT (RT) compared with treatment not including RT (no RT).

Results

A total of 3,853 patients were included in the population of patients treated for BC between 2008 and 2016 with a mean age of 60 years old and a mean follow-up of 5.6 years. In this population, 35 cases of PM were observed, compared with 19.9 expected cases of PM, corresponding to a significant SIR=1.76 (95% CI: 1.22 - 2.39). This excess risk was carried by the RT group of 2973 patients (77% of BC population): 28 observed PM vs 12.9 expected, SIR=2.18 (95% CI: 1.45–3.06). In Cox regression analysis, after adjustment on age, RT was associated with an increased risk of PM compared with no RT, but this result did not reach statistical significance (HR=1.73; p-value=0.21).

Conclusion

Based on our study, BC patients receiving RT appeared to be at higher risk of PM implantation than general female population and BC patients without RT, illustrating a potential association between cardiac exposure during BC RT and conduction disorders.

Funding Acknowledgement

Type of funding sources: None.
Role of a hospital pharmacist in cardiac day procedure ward: a prospective observational study
Authors: Lau G , Rivers G
Published: October 2021

Background

The cardiac day procedure ward provides peri-procedural care to elective patients attending hospital for a broad range of diagnostic and interventional cardiac catheterisation procedures. In this acute setting, changes to patients' medication regimen can often occur, however patient-completed questionnaires are often inaccurate.1,2 Australian standards recommend that an accurate medication history be obtained, and medication reconciliation performed for all patients.3 A plan for cessation and restarting of relevant medications should also be documented.1 However, the role of a pharmacist in this setting has not been widely studied.

Purpose

The aim of this study is to evaluate the role of a pharmacist in a cardiac day procedure ward and identify patient groups who may benefit from a pharmacist medication review.

Methods

A prospective, observational study was conducted over 5 weeks (24/2/20–27/3/20) in a cardiac day procedure ward at a major tertiary referral centre, in a multi-site Australian metropolitan hospital network. An 8-hour per day clinical pharmacy service was provided to the ward, which is open approximately 12 hours per day.

Results

In the study period, 297 patients presented to the ward, and 79% (234/297) received a pharmacist medication review (a systematic assessment of a patient's medication management to optimise treatment outcomes). Elective day procedures were planned for 247 patients, and in 74% (182/247) a pharmacist documented a best possible medication history (comprehensive list of a patient's prescription and non-prescription medicines using two or more information sources). Medication-related problems were identified in 51 patients, with the majority (79%, 70/89) in patients presenting for coronary angiography. 93% (83/89) of interventions were accepted after discussion with the hospital resident medical officer or interventionalist. The remainder (7%, 6/89) were not enacted as further monitoring of vital signs or cardiologist follow-up was needed. Following their procedure, 155 patients returned to the ward for recovery. A specific plan for continuation, cessation or restarting of medications post-procedure was initially documented for 16% (25/155) of patients by catheterisation laboratory staff, and increased to 90% (140/155) with pharmacist medication review. Prescriptions for medications changes were required in 25% (38/155) of patients, and prescription medication counselling was provided by the pharmacist for all patients.

Conclusion

Pharmacists can optimise medication management of patients in cardiac day procedure wards by obtaining an accurate medication history, identifying medication related problems, and documenting a post-procedure medication plan; particularly for patients presenting for coronary angiography. While this study supports the embedding of a clinical pharmacy service in cardiac day procedure wards, more research is needed to fully elucidate the impact on patient outcomes.

Funding Acknowledgement

Type of funding sources: None.
A smartwatch as a rhythm monitor in prehospital emergency care
Authors: Cobos Gil M A
Published: October 2021

Background

A ubiquitous, portable rhythm monitor would be potentially useful in out of hospital emergencies. Smartwatches with ECG capability (SW-ECG) can obtain a single lead ECG similar to lead I.

Purpose

We propose a new method to use the SW-ECG to monitor cardiac rhythm when attending cardiac emergencies in the prehospital setting

Methods

The SW-ECG is used as shown in the figure. The explorer grabs the left hand of the patient and the back of the watch and touches the face of the patient with the watch crown. A record of the difference of potential between the head and the left arm is obtained. The EC lead so formed (head – left arm (HL)) is quite similar to lead I, and can be used to explore the cardiac rhythm in a patient.

In 15 volunteers we recorded the I and HL leads using an SW-ECG. The records were compared for diagnostic accuracy.

Results

In all cases, the records were qualitatively similar (see figure). There was an excellent correlation between the heart rate measured by the two procedures (R2=0,92). All the abnormalities present in lead I (1 case AF, 1 case RBBB, 1 case LBBB, 1 case frequent premature ventricular contractions) were also evident in the HL lead. The mean time required to obtain a diagnostic record was 3.9 seconds.

Conclusion

We propose a quick, simple method to use the SW-ECG to assess heart rhythm in out of hospital emergencies. SW-ECG

Funding Acknowledgement

Type of funding sources: None.
Evidence in crisis: a closer look into the quality of published systematic reviews in the cardiology literature
Authors: Abushouk A , Yunusa I , Elmehrath A O , Elmatboly A M , Saad A , Fayek S H , Abdelfattah O , Ghanem E , Isogai T , Shekhar S , Reed G W , Puri R , Kalra A , Kapadia S R
Published: October 2021

Background

Systematic reviews are usually considered as the highest level of evidence and are increasingly used in shaping cardiology policies and guidelines. However, as the rate of publishing systematic reviews increases annually, there are rising concerns regarding their quality and reporting standards.

Purpose

The current analysis provides an insight into the quality of published systematic reviews in cardiology and provides recommendations for researchers, clinicians, and stakeholders in this regard.

Methods

Using a comprehensive Medline/PubMed search, we retrieved all systematic reviews, published between 2009 and 2019 in five general cardiology journals with the highest impact factor as per the Clarivate Analytics 2019 Journal Impact Factor List (Circulation, European Heart Journal, Journal of the American College of Cardiology, Circulation Research, and JAMA Cardiology). We assessed the methodological characteristics, eligibility criteria, reporting standards, as well as review quality scores according to the AMSTAR tool.

Results

Among 352 retrieved reviews, 275 (75.3%) performed direct head-to-head analysis and 164 (46.6%) included only clinical trials. The median numbers of searched databases and included studies were 3 (IQR: 2, 3) and 13 (IQR: 7, 30). The primary outcomes were often hard clinical endpoints as mortality (39.2%) and stroke (11.9%). 64 (18.2%) registered their protocol, 208 (58.4%) used validated tools for risk of bias assessment, 177 (52.3%) assessed for publication bias, and 221 (62.8%) adhered to the PRISMA checklist. Thirty-five reviews detected significant publication bias, which was significantly associated with heterogeneity of the primary outcome. The AMSTAR quality scores were low or critically low in 71% of evaluated reviews. Further, 87 (24.7%) did not report on whether they received funding or not, 33 (9.4%) reported receiving no funding, and 232 adequately reported on their funding sources [70 (19.9%) from governmental/academic sources, 120 (34.1%) from pharmaceutical companies, and 42 (11.9%) from both sources]. analysis showed that reviews with advanced statistical analysis, those that included RCTs, adhered to the PRISMA checklist, or had higher AMSTAR quality scores had significantly higher citation metrics (p<0.05).

Conclusion

Due to the widespread low quality and poor reporting in cardiovascular systematic reviews, clinicians should be educated on the value of methodological quality in interpreting systematic review findings. In addition, academic societies and guideline writing groups should implement rigorous critical appraisal and peer review policies to improve the synthesis and utilization of systematic reviews in evidence-based cardiovascular medicine.

Funding Acknowledgement

Type of funding sources: None.
STING inhibition in myocardial remodelling following myocardial infarction
Authors: Rech L , Abdellatif M , Poettler M , Stangl V , Ulcar E , Ablasser A , Rainer P P
Published: October 2021

Background

Myocardial infarction (MI) is one of the prevalent causes of death in the world, with some patients developing heart failure from myocardial remodelling after infarction. Inflammatory processes trigger remodelling post-MI. One inflammatory factor is Type 1 Interferon which can be released by cytosolic dsDNA, sensed via the STING-receptor. The aim of this study was to reduce this inflammatory response by inhibiting the STING-receptor and thus reduce post-infarctional remodelling.

Methods

Surgery was performed to trigger infarction for 30 minutes by ligating of the proximal LAD in 22 wildtype male mice (C57BL6/J), another 10 mice have undergone sham operation. Echocardiographic assessment of the endocardial systolic fractional area change (FAC) was carried out before, one day after and three weeks after surgery. The mice with ligation were separated into two groups with eleven individuals each, as well as the sham operated mice in five each group. One group was treated with the STING-Inhibitor while the other received a control substance. Treatment was applied intraperitoneally once per day for three weeks.

Results

– Procedural success was good as evidenced by immediate FAC decline in MI animals.

– One day post-op no significant difference in FAC and infarct size can be seen between the two groups of MI mice

– Three weeks post-op a highly significant difference in FAC can be observed in the group treated with STING-Inhibitor compared to the control group in the MI mice

– The sham operated mice never showed any difference between the groups at any time.

– Fibrosis and Cross sectinal area significantly reduced in treated MI group compared to control

– Ifi44 and Cxcl10 expression levels in the infarct area showed significant reduction in the inhibitor MI group compared to the control MI group after three weeks

Conclusion

STING-Inhibitor potentially improves outcome after a myocardial infarction.

Funding Acknowledgement

Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Research Area Network on Cardiovasczlar Diseases (ERA-CVD) PhD-Program Molecular Medicine - Medical Unviersity of Graz
Attenuated cardiac post-ischemic injury and endothelial dysfunction by stimulation of soluble guanylyl cyclase in red blood cells from patients with type 2 diabetes
Authors: Jiao T , Zhou Z , Mahdi A , Tengbom J , Tratsiakovich Y , Yang J , Pernow J
Published: October 2021

Background

Reduced bioavailability of nitric oxide (NO) contributes to ischemic heart disease in type 2 diabetes (T2D). Red blood cells (RBCs) are known to produce NO bioactivity and to contain a functional soluble guanylyl cyclase (sGC) that is activated by NO. Recent studies revealed that RBCs from patients with T2D exacerbates ischemia-reperfusion (I/R) injury and induces endothelial dysfunction via a mechanism that is dependent on reduced export of NO bioactivity from RBCs. It remains unknown whether stimulation of sGC in RBCs from patients with T2D protects against myocardial I/R injury and endothelial dysfunction.

Purpose

To test the hypothesis that stimulation of sGC in RBCs from T2D patients protects against myocardial I/R injury and improves endothelial function.

Methods

RBCs collected from T2D patients and healthy subjects were incubated with vehicle or the sGC stimulator CYR715 before being administered to isolated Langendorff-perfused rat hearts subjected to 25 min global ischemia and 60 min reperfusion. Left ventricular developed pressure (LVDP) and infarct size were determined. In addition, isolated rat aortic rings were incubated with RBCs subsequent determination of endothelium-dependent relaxation (EDR).

Results

Administration of RBCs from T2D patients impaired post-ischemic recovery of LVDP and induced endothelial dysfunction in comparison with RBCs from healthy subjects (P<0.001). Pre-incubation of RBCs from patients with T2D with CYR715 prior to administration to the isolated heart enhanced the recovery of LVDP (Fig.1A), reduced infarct size (Fig.1B), and attenuated endothelial dysfunction (Fig.1C). CYR715 did not induce cardioprotection in the absence of RBCs. The sGC inhibitor ODQ did not significantly affect cardiac recovery per se but totally abolished the protective effect of CYR715 (Fig.1A).

Conclusions

Stimulation of sGC in RBCs from patients with T2D protects against cardiac I/R injury and prevents development of endothelial dysfunction. Stimulation of the NO-sGC pathway in RBCs appears to be an attractive therapeutic strategy to prevent cardiovascular injury in T2D.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): Swedish Heart and Lung Foundation, the Swedish Research Council
Leadless vs. transvenous single-chamber ventricular pacing in the Micra CED study: 2-year follow-up
Authors: El-Chami Mikhael F , Bockstedt Lindsay , Longacre Colleen , Higuera Lucas , Stromberg Kurt , Crossley George , Kowal Robert C , Piccini Jonathan P
Published: October 2021

Aims 

Clinical trials have demonstrated the safety and efficacy of the Micra leadless VVI pacemaker; however, longer-term outcomes in a large, real-world population with a contemporaneous comparison to transvenous VVI pacemakers have not been examined. We compared reinterventions, chronic complications, and all-cause mortality at 2 years between leadless VVI and transvenous VVI implanted patients.

Methods and results 

The Micra Coverage with Evidence Development study is a continuously enrolling, observational, cohort study of leadless VVI pacemakers in the US Medicare fee-for-service population. Patients implanted with a leadless VVI pacemaker between March 9, 2017, and December 31, 2018, were identified using Medicare claims data linked to manufacturer device registration data (n = 6219). All transvenous VVI patients from facilities with leadless VVI implants during the study period were obtained directly from Medicare claims (n = 10 212). Cox models were used to compare 2-year outcomes between groups. Compared to transvenous VVI, patients with leadless VVI had more end-stage renal disease (12.0% vs. 2.3%) and a higher Charlson comorbidity index (5.1 vs. 4.6). Leadless VVI patients had significantly fewer reinterventions [adjusted hazard ratio (HR) 0.62, 95% confidence interval (CI) 0.45–0.85, P = 0.003] and chronic complications (adjusted HR 0.69, 95% CI 0.60–0.81, P < 0.0001) compared with transvenous VVI patients. Adjusted all-cause mortality at 2 years was not different between the two groups (adjusted HR 0.97, 95% CI 0.91–1.04, P = 0.37).

Conclusion 

In a real-world study of US Medicare patients, the Micra leadless VVI pacemaker was associated with a 38% lower adjusted rate of reinterventions and a 31% lower adjusted rate of chronic complications compared with transvenous VVI pacing. There was no difference in adjusted all-cause mortality at 2 years.
Living systematic reviews in a context of rapidly emerging diseases: challenges and lessons learned
Authors: Iannizzi C , Dorando E , Burns J , Weibel S , Dooley C , Wakeford H , Estcourt LJ , Skoetz N , Piechotta V
Published: October 2021

Background

In a context of a rapid emerging disease, like the COVID-19 pandemic, we are confronted with clinical uncertainty, evolving epidemiological setting and lacking evidence. Within the context of such a high-priority topic, living systematic reviews (LSRs) are an important systematic review type characterized through regular updating and permanent surveillance of continuously evolving evidence. However, with the new pandemic-related challenges, the standard LSR methodology had to be adapted.

Objectives

The objective is to discuss certain challenges that occurred when conducting LSRs in a rapidly emerging disease context. In particular, we give insights in the lessons we have learned from the conduct of two COVID-19 LSRs and highlight emerging methodological aspects.

Results

With the evolving knowledge around the virus and its caused disease, we learned that the initial plan for inclusion of study designs, publication types, interventions and comparators, outcomes and the search strategy had to be adapted. The author teams for example had to revise outcome measures or included observational data in addition to evidence from randomized controlled trials, as they provided substantial information on the safety of investigated interventions. For deciding when to update a LSR, additional aspects, such as policy relevance or waiting for important evidence dependent on the individual research question were considered. To avoid biases in the review process, we learned that transparent reporting of any methodological adaptations is highly relevant; between protocol and review, as well as between each review update.

Conclusions

Our experience showed that LSRs are highly suitable in a pandemic context, in particular when facing unexpected methodological and clinical challenges. The research question, study designs and the methodology, should be revisited and critically discussed before each update, to be flexible enough for addressing the pandemic context.

Key messages

Living systematic reviews are highly relevant in a pandemic context, but the methodology and decision when to update the review have to be adapted to respond purposeful to the emerging topic. To avoid biases in the review process, we learned that transparent reporting of any methodological adaptations is highly relevant; between protocol and review, as well as between each review update.
The impact of COVID-19 in chronic kidney disease stage 5 patients on haemodialysis in Romania
Authors: Steriu A , Buhoara C , Penescu MN
Published: October 2021

Background

CKD 5 is a life threatening condition irrespective of cause. Most patients reach RRT. Predominant therapy is HD. Pandemic preparedness is an important pro-active public health function.

Objectives

1) to describe the incidence of COVID19 and IFR among CKD HD patients; 2) to evaluate the vaccination coverage among HD patients (Jan-Mar 2021); 3) to update a spreadsheet CKD5 HD 12-scenario treatment model by considering two new scenarios based on IFR: before and after vaccination.

Methods

First two objectives use secondary data: JHSU and ECDC (secondary sources of COVID19 data) for Apr 2020-Mar 2021. The 3 NPM periods are: Apr-May 2020 (state of emergency), Jun-Dec 2020 (state of alert; vaccination -), Jan-Mar 2021 (state of alert; vaccination +). Data are taken from the Romanian Renal Registry and population data from Eurostat (available July 2021). IFR was estimated with a modified Kaplan-Meier method (Ghani,2005). A calibrated and validated CKD5 treatment model has previously been defined (10.1093/eurpub/cku161.026). Scenarios are re-run with one parameter adjusted by IFR levels. Analyses used Excel, SPSS.

Results

n = 14300 adult HD patients in March 2020; highest incidence (risk) was recorded in Apr-May 2020: 4.5% (CI95% from 4.1 to 4.8) and 2.5% (CI95% from 2.2 to 2.7). Cumulative incidence was 6.9% vs 18.5 pmp in the general population (period 1). In the general pop COVID19 incidence was highest at 443 pmp in Nov 2020 (period 2). The IFR requires full data validation; CFR was 7.7% (CI95% from 5.97 to 9.46; period 1). It is estimated that by Mar 2021 the IFR has decreased by 50%. Vaccination coverage in HD patients reached 94% (Apr 2021). Preliminary results from the updated model are presented. The model upholds its validity as the IFR allows for a better fine tuning of one parameter (mortality).

Conclusions

treatment need and inequality in service provision can be addressed with a spreadsheet model by including pandemic preparedness measures.

Key messages

Haemodialysis patients had a very high COVID-19 incidence and CFR during the first two months of the COVID-19 pandemic when compared with the incidence in the general population. Pandemic preparedness must include protection measures for patients with chronic diseases. Renal patients are particularly vulnerable given their co-morbidity.
Predictive negative value of the COVID-19 rapid antigen test
Authors: Abroug H , Ben Hassine D , Ben Fredj M , Zemni I , Kacem M , Bouanene I , Belguith Sriha A
Published: October 2021

Background

Testing is a crucial tool in the pandemic response to identify and confirm COVID-19 in those who are symptomatic. The aim of the present study was to assess the negative predictive value (NPV) of COVID-19 Rapid Antigen Testing (RAT) according to the symptoms, test timing in relation to symptom onset and characteristics of the person.

Methods

We performed a prospective cohort study of patients attended the COVID-19 testing center at the university hospital of Monastir, between 23 November 2020 and 19 April 2021. In the first time we performed the COVID19 RAT. In the second time, if this result was negative we performed the reverse transcription polymerase chain reaction (rRT-PCR). The NPV was conducted with SPSS software, version 21.0. A logistic binary regression was performed to determine factors affected the NPV of COVID-19 RAT. A p value of < 0.05 was considered statistically significant.

Results

A total of 855 tests were performed, of which 807 were RAT and 467 rRT-PCR. Positive RAT test was found in 336 cases (39%). False negative RAT was noted in 87 cases (10.2%). The NPV of RAT was 83.6%. The NPV ranged between 80% and 88% for the following symptoms: fever, cough, myalgia, dyspnea, dizziness, asthenia, headache, myalgia, odynophagia, flu_rhume. It varied from 64.2 to 77.8 for Ageusia, Anosmia, Arthralgia, chest pain, thrill, digestive signs. The NPV was equivalent according to age and gender. The NPV varied from 80 to 100% if the test was applied between the first and the 5th day for the onset of symptoms. Beyond this duration, it decreased to 50%. A long period of symptom onset (>5 days) increased significantly the risk of false negative RAT (OR = 2.57 IC95%: [1.38-4.82], p = 0.003).

Conclusions

Many factors may affect the performance of COVID-19 Rapid Antigen Testing (RAT). In fact, negative RAT should be completed by a rRT-PCR according to the the type of symptoms and the time from illness onset.

Key messages

False negative RAT rate was high. Many factors must be taken into account in interpreting the RAT, in particular the type of symptoms and the time from illness onset.
Epidemiology of human alveolar echinococcosis in Armenia
Authors: Manukyan A , Avetisyan L , Sahakyan G , Paez A , Paronyan L , Vanyan A
Published: October 2021

Background

Since the 90s' E.multilocularis infection in foxes is rising and central-eastern European countries had seen first Alveolar echinococcosis (AE) human cases. AE is considered to be a very rare disease in Europe with average incidences of 0.03-0.20/100,000 inhabitants/year. Because of a suitable orography, this study aims to confirm whether there are human AE cases in Armenia, identify areas at risk, and also estimate AE annual incidence.

Methods

Retrospective AE case finding was carried out at main 6 multi-profile medical centers equipped with the most innovative diagnostic means. The medical records of all patients with liver surgery admitted between January 2008 and June 2020 were reviewed. A specific form was developed in EpiInfo v. 7.2. Annual national incidence was estimated using population denominators provided by the National Institute of Statistics (the population of Armenia is estimated at 2 963 243 people).

Results

From September 2019 until June 2020, overall 11 AE cases have been identified. All patients were diagnosed at advanced stages, with subsequent poor prognosis and costly treatment. Confirmation was based on tissue biopsy results. Age ranged from 19-59 years with a median of 39yrs. E. multilocularis was detected in rural communities, mostly in the Gegharkunik region (6 cases, 55%). Annual average incidence of AE was 0.033 varying between 0.032 in 2008 and 0.1 in 2017. For comparison with Armenia, an annual incidence in France was 0.026/100,000 in 2008 (the population of France is estimated at 65 273 511 people).

Conclusions

All cases were not notified by the surveillance system and the real prevalence of AE in the country is unknown. This young age could indicate widespread of infection in animals. Therefore, the burden of AE disease is difficult to estimate. The surveillance system in Armenia can be improved by the development of national guidelines for the prospective registry, AE awareness campaigns.

Key messages

First-time identification of human AE in Armenia calls for implementation of surveillance with a case definition and registry of all cases. AE is an emerging, and so far silent threat in Armenia.
Androgen deprivation therapy and cognitive decline in the NEON-PC study
Authors: Araujo N , Costa A , Conceição-Lopes L , Ferreira A , Carneiro F , Pacheco-Figueiredo L , Morais S , Tedim-Cruz V , Pereira S , Lunet N
Published: October 2021

Background/Objective

Androgen deprivation therapy (ADT) has been associated with cognitive decline, but results have been heterogenous. We describe changes in cognitive performance in patients with prostate cancer (PCa), according to treatment with ADT, during the 1st year after PCa diagnosis.

Methods

Between February 2018 and March 2021, 348 patients with PCa treated at the Instituto Português de Oncologia do Porto were evaluated with the Montreal Cognitive Assessment (MoCA), before treatment and after one year (1y). ADT was used in 183 participants, and 165 were treated without ADT (total prostatectomy, radiotherapy, brachytherapy, active surveillance). Cognitive decline was defined as the decrease in MoCA from baseline to the 1y-evaluation below 1.5SD of the distribution of the MoCA variation in the whole cohort. Participants scoring below age- and education-based normative reference values in MoCA were considered to have probable cognitive impairment (PCI). Multivariate logistic regression was used to estimate age- and education-adjusted OR (aOR) of the association between ADT and cognitive decline/incident PCI.

Results/Discussion

PCI was observed in 12.4% of the patients at baseline. Mean MoCA scores increased from baseline to the 1y-evaluation (22.4 vs. 22.9, p = 0.001), and 51.2% of PCI cases at baseline had normal MoCA scores at 1y. Cognitive decline was most frequent in the ADT group (9.3% vs. 3.6%, p = 0.034), although the aOR was 2.44 (95%CI:0.89-6.71). The 1yr cumulative incidence of PCI was 10.4% (95%CI:6.2%-16.2%) in the ADT-group and 2.8% (95%CI:0.8-%-7.1%) in the non-ADT group [aOR=3.15 (95%CI:0.97-10.25)].

Conclusions

ADT was associated with a decrease in the cognitive performance of PCa patients during the 1st year after diagnosis. The completion of the 1y-evaluation in the whole cohort (n = 600) is needed to confirm these preliminary results.

Funding

POCI-01-0145FEDER-032358;PTDC/SAU-EPI/32358/2017; UIDB/4750/2020;SFRH/BD/119390/2016

Key messages

Half of the cases with cognitive impairment at baseline improved at one-year. Patients treated with ADT seem to be affected by cognitive decline more frequently.
Vegetable gardening in slum homes for food security especially in COVID-19 and well-being in India
Authors: Agarwal S , Verma N , Verma S , Vishvakarma K , Kothiwal K
Published: October 2021

Issue

With livelihood loss, uncertain earning, slum families are often food insecure, at risk of undernutrition particularly during COVID-19 in Indian and other LMIC cities. While wheat flour was provided free during lockdown, later at subsidized costs and during non-COVID times, vegetables need to be bought at market price.

Methods

UHRC provided seeds, encouraged families to grow vegetables in slums of Indore, India for five years. In 2019-20 and 20-21, data was gathered through interviews, observations in 20 slums (where >15 families grew vegetables).

Results

Uptake of seeds increased from 900 families in 2019-20 to 1200 in 20-21. With sharing of surplus harvest, 70,000 persons benefited in 2020-21. Families overcame food insecurity by arranging just wheat flour and cooked a vegetable for a meal. Used paint tubs, broken buckets and small spaces were used. Creepers were made to climb on roofs, walls, trees. Green cover increased to > 8 acres in 2021. The practice saves valuable family resources particularly in COVID-19 distress through provision of vegetables for family consumption.

Lessons

Perseverant efforts are key and help build a ‘fairer, healthier world'. Yield per family increased as they grow with incremental confidence. Despite small spaces slum families creatively grew vegetables. Children and youth help overcome constraints and are key actors. Early adopters serve as motivators and champions for subsequent adopters who begin growing vegetables on observing neighbours, friends grow vegetables and share with them. Nurturing plants, seeing vegetables grow fostered positivity, hope, motivation to grow every year, enhanced self-worth, and a positive feeling about their abode. People particularly children and youth learn how eating home-grown vegetables reduces carbon footprint of purchased vegetables transported to urban markets, save cost and overcome food insecurity. They reduce ambient air temperature to cool urban spaces.

Key messages

Despite small spaces, slum families grow, share vegetables, feel accomplished, enable food security, social cooperation, all crucial to well-being of slum populations. Methods used and lessons learnt of perseveringly motivating slum families have the potential of replication/adaptation in cities of India and other LMICs.
Household pharmaceutical waste (example from Serbia)
Authors: Paut Kusturica M , Ostojic T , Kresoja M , Horvat O , Tomas A , Jevtic M
Published: October 2021

Background

Proper disposal of household pharmaceutical waste can reduce the negative influence of medicines on the environment. Environmental awareness do not necessarily equate with proper behavior, as other issues, such as the availability of an organized disposal system, play an important role. The aim was to examine the current disposal methods of unused medicines from households, and the willingness of Serbian residents to participate and bear the costs of an organized collection program. Also, we wanted to define factors contributing to an individual's willingness to participate and pay for a disposal program.

Methods

The survey included randomly selected patients older than 18 years visiting private pharmacies in the four largest Serbian cities. The questionnaire included information on the presence of unwanted medicines in the household, general medicine disposal practices, the likelihood to participate in a medicine takeback program, willingness to pay for a disposal program, importance to the environment, and demographic variables.

Results

The majority of Serbian people dispose unused medicines into household garbage. 80% of respondents are likely to participate, however less than half are willing to pay for the collection of unused medicines. The factors that influenced willingness to participate are environmental awareness and income, while the factors affecting willingness to pay, are previously received advice about proper disposal, education level, number of unwanted medicines in the household and gender.

Conclusions

Awareness campaigns advising the general public on proper medicine disposal and well-organized and easily accessible collection programs are essential in order to enable the general public to return unused medicines for proper disposal.

Key messages

Household pharmaceutical waste is a major public health issue in Serbia. Residents in Serbia are willing to participate in collection programs, thus building legislative into practice is urgent.
A2CT Assessment Alzheimer Centre Tool: evaluation tool of structures for people with dementia
Authors: Mangili S , Brambilla A , Capolongo S
Published: October 2021

Background

The increasing number of elderly population (17,4% over 65 in Europe in 2009 and 20,3% in 2019) is following by the progressive growth in diseases related to age. One of them is dementia that afflicts 8% of over 65s, of which 60% with Alzheimer. Patients with progressive cognitive deterioration often need to leave their houses and move to nursing homes but in many cases, these aren't suitable for hosting them because based on regulations and standards that are exceeded. Aim of the study is to evaluate if those territorial structures are suitable for patients.

Methods

The study addressed a systematic literature review, in the relationship between built environment and patients with dementia, different case studies, and existing evaluation tools. The evidence that emerged allowed to develop of a rating tool divided into 4 macro-areas (quality, spaces, activities, and wayfinding) and composed by different criteria and indicators. The tool was applied in 5 facilities in Northern Italy and strategies were provided.

Results

The facilities differ in type and age of construction and the results of the evaluation tool show that 2 are inadequate (<60%) 2 sufficient (<80%) and 1 excellent (>80%). The best one is the newest and is conceived based on analysis of evidence in the relationship between Alzheimer's and built environment and facts this scored the maximum (100%) for spaces than the other older structures, made by the reuse of existing spaces, results as inadequate (every structure obtained <65%). For each criticality found implementation strategies were provided.

Conclusions

The investigation highlights that the design of territorial structures must be based on evidence to create better spaces for the well-being of patients. It also shows that existing buildings are not able to respond to the need of patients affected by dementia. To get a broader view of the situation, the tool could be applied in other structures both in other regions and abroad.

Key messages

This research is the first that use assessment methodologies for the quality evaluation of territorial structures dedicated for Alzheimer patients in the Italian context. Evaluating a structure and adapting it to the needs of the specific patient must become the practice in a constantly evolving field such as the medical-health one.
Urgency and emergency process for ambulance regulation during the COVID-19 pandemic
Authors: Mafra ACCN , Gomes WPP , Domingues J , Oliveira IE , Trufelli AM , Brito KLD , Bottaro PV , Palácio DC , Martins ACF
Published: October 2021

Issue

Severe acute respiratory syndrome (SARS) caused by SARS-CoV-2 proved to be a global public health problem. Critical ill patients attended in Primary Health Care (PHC) often require fast transportation to the Urgency and Emergency Network (UEN). Controlling an ambulance fleet requires technical skill, discipline, organization and emotional care. During the pandemic, there was an increase in ambulances requests, including removing patients from PHC to the UEN. In this context, ambulances were occasionally lost or not directed to PHC facilities, resulting in worsening the patient clinical situation, dropout or long waiting periods.

Description of the problem

To strengthen the removals process and patients referrals, PHC and UEN professionals of services in São Paulo designed and implemented a strategy according to patient severity criteria. We used a 5W2H matrix to discuss relevant topics, skills, actions and indicators and develop a tool to prioritize diagnoses or clinical conditions requiring immediate removal. Besides, we standardized the request flows and drivers contact. The team trained professionals to manage ambulances. We monitor the quantity, destination and release time of ambulances.

Results

We defined acute myocardial infarction, stroke, sepsis, SARS and pregnancy as a priority for removal. During implantation, removals volume increased from 18 to 50 per week. Despite this, there was no change in the average waiting time: about 82 minutes. The dropout rate and release time slightly increase, from 2.4% to 3.0% and from 28 minutes to 43 minutes per request, respectively. Besides technical issues, professionals were oriented to manage anxiety. It was possible to evaluate the demand for hiring more vehicles and save resources.

Lessons

This experience strengthened PHC as an access point and organizer of the healthcare network. Early detection of UEN referral necessity contributes to providing adequate, equity and timely care.

Key messages

In the face of the COVID-19 pandemic scenario, a strategy to organize and optimize removal to UEN is needed to assure adequate and timely care. Cooperation between different services in the health care network promotes safety and quality of patient care.
Rabies surveillance in the central region of Tunisia: A 15-year observational study
Authors: Ben Nasrallah C , Ben Fredj M , Kacem M , Grira S , Dhouib W , Zemni I , Abroug H , Bouanene I , Belguith Sriha A
Published: October 2021

Background

Rabies remains a major public health threat in many parts of the world and is responsible for an estimated 55,000 human deaths annually. In Tunisia, the National Rabies Control Program was initiated in 1982 based on dog's annual vaccination campaign. The aim of our study was to describe the epidemiological profile and management of rabies exposure in the Monastir governorate, Tunisia.

Methods

We included in our study all cases of animal aggression reported between 2004 and 2018 in the Monastir governorate. The source of the data was the directorate of primary health care in Monastir.

Results

A total of 27,277 bites were reported with an annual average of 1,817 cases per year. Most of victims were in the 5-14 age group (25%, n = 6,902). The culprit animal was the dog in 64% of cases followed by rats and cats. Only 42% of attacking dogs were vaccinated. A significant increase in dog bites was noted from 2004 to 2018 (β = 16.5; p = <10-3). The number of bites increased significantly (β = 23.2; p = <10-3) by vaccinated dogs and decreased significantly by unvaccinated dogs (β = -12; p = <10-3). During our study period, a total of 146 cases of animal rabies was confirmed. Only one case of human rabies was reported, the aggressor animal was a cat and post-exposure prophylaxis was not received.

Conclusions

In Tunisia, human exposure to rabies by a dog has been on the rise. Future interventions should focus on mass dog vaccination campaigns and contraception in order to eliminate this disease.

Key messages

A significant increase in dog bites was noted from 2004 to 2018. It is crucial to reinforce appropriate preventive strategies, such as mass dog vaccination programs.