COVID-19: from epidemiology to treatment.

The COVID-19 pandemic has greatly impacted the daily clinical practice of cardiologists and cardiovascular surgeons. Preparedness of health workers and health services is crucial to tackle the enormous challenge posed by SARS-CoV-2 in wards, operating theatres, intensive care units, and interventionist laboratories. This Clinical Review provides an overview of COVID-19 and focuses on relevant aspects on prevention and management for specialists within the cardiovascular field.

An Update on Heart Transplantation in Human Immunodeficiency Virus-Infected Patients.

Cardiovascular diseases have become a significant cause of morbidity in patients with human immunodeficiency virus (HIV) infection. Heart transplantation (HT) is a well-established treatment of end-stage heart failure (ESHF) and is performed in selected HIV-infected patients in developed countries. Few data are available on the prognosis of HIV-infected patients undergoing HT in the era of combined antiretroviral therapy (cART) because current evidence is limited to small retrospective cohorts, case series, and case reports. Many HT centers consider HIV infection to be a contraindication for HT; however, in the era of cART, HT recipients with HIV infection seem to achieve satisfactory outcomes without developing HIV-related events. Consequently, selected HIV-infected patients with ESHF who are taking effective cART should be considered candidates for HT. The present review provides epidemiological data on ESHF in HIV-infected patients from all published experience on HT in HIV-infected patients since the beginning of the epidemic. The practical management of these patients is discussed, with emphasis on the challenging issues that must be addressed in the pretransplant (including HIV criteria) and posttransplant periods. Finally, proposals are made for future management and research priorities.

Burnout in ENT France: Update and risk factors; a STROBE analysis.

BACKGROUND: Burnout can significantly impact practitioners and their co-workers, and hence patients. There are no data for the prevalence of burnout in French ENT specialists, or for associated risk factors. MATERIAL AND METHODS: A French national cross-sectional online survey was performed on the initiative of the ENT National Professional Council (CNPORL), contacting all ENT specialists whose e-mail address was known to the French Society of ENT, the National Professional Council or the National ENT Union. The 22-question Maslach Burnout Inventory (MBI) was sent out, along with 16 extra questions on possible risk factors. OBJECTIVES: The study sought to assess the prevalence and severity of burnout, using the MBI, and to analyze risk factors. RESULTS: Among the 1936 physicians, 406 contacted responded to the questionnaire (21%). Mean age was 47±14 years (range, 25-77 years); 53% male, 47% female. 196 (48%) reported burnout, including 20 (5%) severe burnout. Independent risk factors for burnout of whatever severity, comprised social interaction issues, history of identified burnout, and medicolegal pressures. Social interaction issues were independently associated with specifically severe burnout. CONCLUSIONS: Burnout affected almost half of respondents. There are identifiable risk factors, for which improvements could be implemented.

French-language questionnaires in ENT: Inventory and review.

OBJECTIVE: Patient-Reported Outcome Measures (PROMs) are now an integral part of clinical and academic practice in ENT, and it is essential to have tools with a validated French version. However, there are no guidelines on ENT questionnaires available in French or those that could have transcultural adaptation. METHODS: The present study, under the auspices of the ENT National Professional Council and the French Society of ENT, inventoried PROMs, for each super-specialty and pathology, meeting one of the following inclusion criteria: validated French version, not translated but used internationally (i.e., translated into other languages and widely cited since 2017), or subjectively deemed useful by experts in the super-specialty in question. RESULTS: In total, 103 questionnaires were identified. To encourage and accompany their intercultural adaptation and statistical validation, this article presents the rationale and methodology of such an undertaking. CONCLUSION: PROMs either already validated in French or which it would be useful to translate were inventoried. The methodology of translation and validation to guarantee reliability and relevance is presented.

Evaluation of antiretroviral-related errors and interventions by the clinical pharmacist in hospitalized HIV-infected patients.

OBJECTIVES: The aim of the study was to identify antiretroviral-related errors in the prescribing of medication to HIV-infected inpatients and to ascertain the degree of acceptance of the pharmacist's interventions. METHODS: An observational, prospective, 1-year study was conducted in a 750-bed tertiary-care teaching hospital by a pharmacist trained in HIV pharmacotherapy. Interactions with antiretrovirals were checked for contraindicated combinations. Inpatient antiretroviral prescriptions were compared with outpatient dispensing records for reconciliation. Renal and hepatic function was monitored to determine the need for dose adjustments. RESULTS: The prescriptions for 247 admissions (189 patients) were reviewed. Sixty antiretroviral-related problems were identified in 41 patients (21.7%). The most common problem was contraindicated combinations (n=20; 33.3%), followed by incorrect dose (n=10; 16.7%), dose omission (n=9; 15%), lack of dosage reduction in patients with renal or hepatic impairment (n=6; 10% and n=1; 1.7%, respectively), omission of an antiretroviral (n=6; 10%), addition of an alternative antiretroviral (n=5; 8.3%) and incorrect schedule according to outpatient treatment (n=3; 5%). Fifteen out of 20 errors were made during admission. A multivariate analysis showed that factors associated with an increased risk of antiretroviral-related problems included renal impairment [odds ratio (OR) 3.95; 95% confidence interval (CI) 1.39-11.23], treatment with atazanavir (OR 3.53; 95% CI 1.61-7.76) and admission to a unit other than an infectious diseases unit (OR 2.50; 95% CI 1.28-4.88). Use of a nonnucleoside reverse transcriptase inhibitor was a protective factor (OR 0.33; 95% CI 0.13-0.81). Ninety-two per cent of the pharmacist's interventions were accepted. CONCLUSION: Antiretroviral-related errors affected more than one-in-five patients. The most common causes of error were contraindicated or not recommended drug-drug combinations and dose-related errors. A clinical pharmacist trained in HIV pharmacotherapy could help to detect errors and reduce the duration of their effect.

Tocilizumab reduces the risk of ICU admission and mortality in patients with SARS-CoV-2 infection.

OBJECTIVE: In some patients the immune response triggered by SARS-CoV-2 is unbalanced, presenting an acute respiratory distress syndrome which in many cases requires intensive care unit (ICU) admission. The limitation of ICU beds has been one of the major burdens in the management around the world; therefore, clinical strategies to avoid ICU admission are needed. We aimed to describe the influence of tocilizumab on the need of transfer to ICU or death in non-critically ill patients. METHODS: A retrospective study of 171 patients with SARS-CoV-2 infection that did not qualify as requiring transfer to ICU during the first 24h after admission to a conventional ward, were included. The criteria to receive tocilizumab was radiological impairment, oxygen demand or an increasing of inflammatory parameters, however, the ultimate decision was left to the attending physician judgement. The primary outcome was the need of ICU admission or death whichever came first. RESULTS: A total of 77 patients received tocilizumab and 94 did not. The tocilizumab group had less ICU admissions (10.3% vs. 27.6%, P=0.005) and need of invasive ventilation (0 vs 13.8%, P=0.001). In the multivariable analysis, tocilizumab remained as a protective variable (OR: 0.03, CI 95%: 0.007-0.1, P=0.0001) of ICU admission or death. CONCLUSIONS: Tocilizumab in early stages of the inflammatory flare could reduce an important number of ICU admissions and mechanical ventilation. The mortality rate of 10.3% among patients receiving tocilizumab appears to be lower than other reports. This is a non-randomized study and the results should be interpreted with caution.

[Analysis of the duration of and reasons for changing the first combination of antiretroviral therapy]. / Análisis de la duración y los motivos de cambio de la primera combinación de tratamiento antirretroviral.

OBJECTIVE: To determine the duration of and reasons behind changing the various combinations of drugs used for the initiation of antiretroviral treatment in naïve patients. METHODS: A retrospective observational study that included all patients with HIV infection who started antiretroviral therapy in a high-tech university reference hospital during the period from 1 January 2003 and 31 December 2005. Patients were followed until 31 December 2008. To estimate the cumulative probability of discontinuation the Kaplan-Meier method was used. RESULTS: A total of 441 patients were included. The average duration of the first treatment was 384 (interquartile interval 84-1290) days. The regimen based on non-nucleoside reverse transcriptase inhibitors and those that included as nucleosides abacavir or tenofovir in combination with lamivudine or emtricitabine showed a significantly longer duration than the rest. The main reasons for termination were the side effects, although in a lesser percentage than that obtained in previous studies. No associations were found between the rest of the characteristics of the patients or of the treatment and the risk of termination. DISCUSSION: Although the duration of the first antiretroviral treatment remains short, currently fewer changes are made due to side effects and due to loss to follow-up. The reasons may be better tolerance and less complexity. However, more studies are needed to determine the benefits of one regimen or another, and to be able to generalise the results.

Thalidomide in refractory and relapsing multiple myeloma.

Patients with multiple myeloma (MM) refractory to chemotherapy can only benefit from supportive measures and have a very short survival. Thalidomide has recently shown antitumor activity in patients with refractory myeloma. Twenty-three patients (12 men and 11 women; median age, 72 years) with advanced MM were treated with thalidomide. Sixteen patients had refractory disease and seven had untested relapse. The median dose of thalidomide was 400 mg d (range, 200 to 800 mg/d). The drug was generally administered in two divided doses. Five patients required treatment discontinuation because of toxicity. Twelve of 23 patients (52%) responded. Three (13%) achieved a partial response, with greater than 50% reduction in serum monoclonal (M)-protein levels, and nine (39%) attained a minimal response, with a greater than 25% decrease in serum M-protein levels. No decrease in the size of soft tissue plasmacytomas was observed in six patients with extramedullary involvement.

Perioperative antibiotic prophylaxis in Spanish hospitals: results of a questionnaire survey. Hospital Pharmacy Antimicrobial Prophylaxis Study Group.

A questionnaire survey was sent to a random sample of the Spanish network of National Health System public acute-care hospitals. Of responding institutions (representing 25% of Spanish hospital beds), nearly 75% had active surveillance programs for the prevention and control of surgical-site infections (SSIs), but only 20% performed postdischarge surveillance. Overall, perioperative antibiotic prophylaxis (PAP) was used in 84% of all surgical procedures. For 77% of procedures, there were written guidelines for the choice and use of PAP. Cefazolin was the most commonly used antibiotic (38%). Duration of PAP was shorter than 24 hours in 75% of procedures, and only a single dose was given in 52% of procedures. PAP was commonly used in breast (52%) and inguinal hernia repair (69%) procedures, as well as in laparoscopic abdominal surgery (86%). In summary, the use of PAP in Spanish hospitals is adequate, but improvements can be made in the frequency of prolonged PAP and in the use of broad-spectrum antibiotics. Surveillance systems for SSI, including postdischarge follow-up, also should be improved.

[Comparative study of an expert system application in the prescription of medications]. / Estudio comparativo de la aplicación de un sistema experto en la prescripción de medicamentos.

BACKGROUND: The aim of this study was to evaluate the impact of a expert drug system implementation on the drug prescription habits and on drug cost in an university hospital. MATERIAL AND METHODS: During a 3 months period, the drug prescriptions to patients admitted to the Internal medicine, lung, gastroenterology and hepatology units, have been evaluated through the expert drug system (Medisource). This expert drug system functions in according to patients characteristics such as age, weight, height, sex, renal function and liver function. It recommends the correct dose, detects interactions and adverse effects and makes suggestions in pregnancy and lactation. It also offers alternative drugs with their cost. During the study period physicians were unaware of the investigation being performed. RESULTS: 836 patients (63.9 +/- 16.5 years) with an average hospital stay length of 11.6 +/- 6.7 days were studied. The most common diagnoses were: lung obstructive chronic disease, cirrhosis, gastrointestinal hemorrhage and cancer. The total amount of drug prescribed was 6,308. The expert system detected 458 overdosages and 33 underdosages, mainly in antibiotics and antiulcer drugs, and 1,722 interactions. The drug costs reduction that could be obtained following the expert system recommendations was 4.5% in antibiotic drugs and 23% in antiulcer drugs. CONCLUSION: The frequency of drug overdosage and underdosage in patients admitted in an university hospital is relatively high. The expert systems available for drug decisions could solve this problem.

[Vancomycin and teicoplanin use as antibiotic prophylaxis in cardiac surgery: pharmacoeconomic study]. / Vancomicina y teicoplanina como profilaxis antibiótica en cirugía cardíaca: estudio farmacoeconómico.

BACKGROUND: To assess the economical impact of vancomycin use versus teicoplanin use as antibiotic prophylaxis for patients undergoing cardiac surgery for valve replacement (VR) and coronary artery by-pass (CABS) procedures. PATIENTS AND METHODS: This is an ancillary cost minimization analysis of a double blinded, parallel groups, randomised clinical trial (RCT), with the main objective of comparing the safety and efficacy of these antibiotics. 500 patients were included in the study; 267 in the CABS group and 233 in the VR group. The CABS patients received 1 g vancomicin or 400 mg teicoplanin, plus 150 mg netilmicin. The VR group received a second dose of each drug after extracorporeal circulation. In order to calculate the costs we considered the direct cost of the drug, the i.v. mix and the administration costs, together with personnel and structure costs. We considered two different situations: the administration of drugs within the surgical room theatre and in the medical ward. RESULTS: The demographic data of both groups were comparable. The frequency of severe adverse drug reactions (ADR) were similar (0.4%) in both groups, as well as the post-operative infection rates (8.6%). Differences were seen in the frequencies of low severity ADRs: 20.4% in the vancomycin group and 1.6% in the teicoplanin group. When the antibiotics were administered in the surgical room, among CABS patients the costs were 8,265 pts. for the teicoplanin group and 12,005 pts. for the vancomycin group; while among VR patients, costs were respectively 11,661 pts. and 14,528 pts. Administration costs of teicoplanin and vancomycin within a medical ward setting, however, the costs were 6,740 pts. and 2,809 pts. for CABS patients, and 5,308 pts. and 10,140 pts. for VR patients, respectively. CONCLUSIONS: The costs of antibiotic prophylaxis among cardiac surgery patients heavily depends on the setting and circumstances of drug administration. The minimization cost analysis indicates that teicoplanin is the most cost-effective option if the drug is administered within the surgical area, while vancomycin is the less costly option when administered within the medical ward. However, if the second option is to be chosen, it is necessary to assure the right plasmatic drug levels of the antibiotic at the beginning of the surgical procedure.

[Ichthyosis X. Clinical review and rapid identification using lipid electrophoresis]. / Ictiosis X. Revisión clínica e identificación rápida por electroforesis de lípidos.

Ichthyoses X as a part of the steroid sulphatase deficiency syndrome are reviewed. The usefulness of lipid electrophoresis is emphasized.

Simultaneous pancreas-kidney transplantation in HIV-infected patients: a case report and literature review.

Since the introduction of combined antiretroviral therapy (cART), solid organ transplantation (SOT) has become a therapeutic option for the HIV-positive population. In contrast with liver and kidney transplantation, only three simultaneous pancreas-kidney transplants (SPKT) have been reported among HIV-infected patients. Herein we have reported the first SPKT in an HIV-infected patient in Spain. The pancreas graft failed at 2 weeks and the patient died at 9 months because of a Pseudomonas aeruginosa infection. The three recipients reported in the literature lived, despite the failure of both the pancreas and kidney grafts in one subject. Despite the poor outcome of our case, HIV-1 infection was controlled after transplantation (stable CD4(+) cells and no AIDS-related events), and the kidney graft functioned with no episodes of rejection. The cART regimen used in the pretransplant period was switched at the time of transplantation to raltegravir and two nucleoside reverse transcriptase inhibitors (NRTI). Raltegravir has no interactions with immunosuppressive drugs. Target plasma levels of tacrolimus were achieved at a dose similar to that used in HIV-negative transplant recipients. The most adequate antiretroviral regimen for HIV-infected SOT recipients has not yet been established; however, one may consider switching protease inhibitors or non-NRTI-based regimens for a raltegravir-based regimen at the time of transplantation.

Relationship between adherence level, type of the antiretroviral regimen, and plasma HIV type 1 RNA viral load: a prospective cohort study.

The relationship between adherence, antiretroviral regimen, and viral load (VL) suppression was assessed through a 1 year prospective follow-up study among 1142 HIV-infected patient. Patients on antiretroviral therapy who attended to the pharmacy during a 6-month period were considered eligible. Those included in the final analysis were patients who had been taking the same antiretroviral therapy for > or =6 months since their inclusion. The cohort included patients taking first line therapy (n = 243) and antiretroviral-experienced patients (n = 899). Naive patients who were included had to have reached undetectable VL at enrollment. Antiretroviral-experienced patients with detectable VL determinations in the previous 6 months were excluded. Adherence was measured by means of announced pill counts and dispensation pharmacy records. Of patients, 58% were taking NNRTI, 31.4% boosted PI, and 10.6% unboosted PI-based regimens. Overall, the relative risk of virologic failure was 9.0 (95% CI 4.0-20.1) in patients with adherence 80-89.9%, 45.6 (95% CI 19.9-104.5) with adherence 70-79.9%, and 77.3 (95% CI 34.2-174.9) with adherence <70%, compared with adherence of > or =90%. The risk of virologic failure in patients with adherence <90% taking unboosted PI was 2.5 times higher than the group taking boosted PI (95% CI 1.2-5.3). There were no statistical differences in patients taking boosted PI and those who were taking NNRTI. Less than 95% of adherence is associated with high virologic success. For patients taking NNRTI- or boosted PI-based regimens with adherence rates of 80%, the failure rate is <10%. These data do not affect the goal of achieving the highest level of adherence possible.

Treatment with the insulin analogue lispro in children and adolescents with type 1 diabetes mellitus: evaluation over a 3-year period.

The aim of the present study was to evaluate the degree of metabolic control obtained with the use of the insulin analogue lispro compared to the previous regimen with classical regular insulin in children and adolescents with Type 1 diabetes mellitus. HbA1c, lipid metabolism, body mass index (BMI), frequency of severe hypoglycaemia, carbohydrate intake, total daily insulin requirements and its distribution during the day were analysed in 44 diabetics patients (57% males and 43% females) throughout a 3-yr period. The mean age of the patients at the beginning of the study was 15.6 +/- 2.7 yr with a mean duration of the disease of 8.01 +/- 3.4 yr. All data were evaluated for the year before the change of treatment, and 1 yr (44 patients), 2 yr (19 patients) and 3 yr (13 patients) after the change. HbA1c levels did not significantly change (6.6 +/- 1.1% with regular insulin, 6.32 +/- 1.05% in the 1st year with lispro, 6.6 +/- 1.1% in the 2nd yr with lispro, 6.33 +/- 0.9% in the 3rd yr with lispro). However, significant differences (p = 0.03) were found after 3 yr of treatment in those patients who changed to insulin lispro therapy due to a bad glycaemic control. The total daily insulin dose (U/kg/d) remained unchanged. The total short-acting/intermediate-acting insulin ratio significantly decreased (45.9 +/- 0.1% regular insulin; 37.2 +/- 0.1% 1st yr lispro (p < 0.001); 33.6 +/- 0.1% 2nd yr lispro (p < 0.05); 35.5 +/- 0.1% 3rd yr lispro (p < 0.05). BMI and lipid profile remained unchanged. The self-reported daily carbohydrate in take significantly decreased due to a reduction of snacks. Total number of episodes of severe hypoglycaemia did not change significantly. In conclusion insulin lispro treatment did not modify the daily insulin dose, but reduced the short-acting/intermediate acting insulin ratio. The metabolic control remained unchanged. The number of patients reporting severe hypoglycaemia was similar despite the treatment schedule. After this 3-yr duration trial all patients decided to continue the treatment with lispro insulin.

Acrocyanosis induced by interferon alpha(2a).

A 56-year-old woman with mycosis fungoides developed acrocyanosis each time treatment with interferon alpha(2a) was started. Acrocyanosis disappeared after discontinuing therapy. Immunological study performed while acrocyanosis was present showed elevated antinuclear antibody (ANA) titers and circulating immune-complex levels. Long-term interferon treatment has been related to autoimmune side effects. Raynaud's phenomenon has been observed in patients undergoing interferon treatment associated with elevated ANA titers, to cryoglobulinemia or to arterial occlusion. Acrocyanosis has never before been described as side effect in patients undergoing this treatment. We believe that our patient's acrocyanosis must be considered a side effect of interferon.

Thalidomide in multiple myeloma: lack of response of soft-tissue plasmacytomas.

Thalidomide is active in patients with refractory myeloma. Seventeen patients (nine men/eight women, median age 73 years) with multiple myeloma (MM) were treated with thalidomide. Fifteen patients had refractory disease and two untested relapse. The median dose of thalidomide was 500 mg (range, 200-800 mg). Nine of the 17 patients (53%) responded. The response rate was significantly higher in patients with no extramedullary disease than in those with soft tissue masses (75% CI: 43-95% versus 0%; P = 0.01)). Of note, no decrease in the size of soft tissue plasmacytomas was observed in all the five patients who had extramedullary involvement. This data suggests that the mechanism of action and effectiveness of thalidomide might depend on the site of the tumour cells.