Interactions listed in the Paxlovid fact sheet, classified according to risks, pharmacological groups, and consequences.

Paxlovid (nirmatrelvir plus ritonavir) is a new oral antiviral therapeutic for the treatment and post-exposure prophylaxis of COVID-19. Nirmatrelvir is an inhibitor of SARS-CoV-2 main protease, while ritonavir is used as a CYP3A inhibitor in low doses to slow the metabolism of nirmatrelvir, thus enhancing their therapeutic effect. The isoenzyme CYP3A4 is responsible for at least part of the oxidative metabolism of approximately 60% of available medications and ritonavir is therefore a significant source of drug interactions. We describe here the drugs that are contraindicated or should be used with or without precautions when Paxlovid (nirmaltrevir plus ritonavir) should be administered according to each fact sheet in force at the Spanish Agency for Medicines and Health Products.

Decalogue for the selection of oral antibiotics for lower respiratory tract infections.

Lower respiratory tract infections, including chronic obstructive pulmonary disease exacerbations (COPD-E) and community acquired pneumonia (CAP), are one of the most frequent reasons for consultation in primary care and hospital emergency departments, and are the cause of a high prescription of antimicrobial agents. The selection of the most appropriate oral antibiotic treatment is based on different aspects and includes to first consider a bacterial aetiology and not a viral infection, to know the bacterial pathogen that most frequently cause these infections and the frequency of their local antimicrobial resistance. Treatment should also be prescribed quickly and antibiotics should be selected among those with a quicker mode of action, achieving the greatest effect in the shortest time and with the fewest adverse effects (toxicity, interactions, resistance and/or ecological impact). Whenever possible, antimicrobials should be rotated and diversified and switched to the oral route as soon as possible. With these premises, the oral treatment guidelines for mild or moderate COPD-E and CAP in Spain include as first options beta-lactam antibiotics (amoxicillin and amoxicillin-clavulanate and cefditoren), in certain situations associated with a macrolide, and relegating fluoroquinolones as an alternative, except in cases where the presence of Pseudomonas aeruginosa is suspected.

Recommendations for use of antigenic tests in the diagnosis of acute SARS-CoV-2 infection in the second pandemic wave: attitude in different clinical settings.

The high transmissibility of SARS-CoV-2 before and shortly after the onset of symptoms suggests that only diagnosing and isolating symptomatic patients may not be sufficient to interrupt the spread of infection; therefore, public health measures such as personal distancing are also necessary. Additionally, it will be important to detect the newly infected individuals who remain asymptomatic, which may account for 50% or more of the cases. Molecular techniques are the "gold standard" for the diagnosis of SARS-CoV-2 infection. However, the massive use of these techniques has generated some problems. On the one hand, the scarcity of resources (analyzers, fungibles and reagents), and on the other the delay in the notification of results. These two facts translate into a lag in the application of isolation measures among cases and contacts, which favors the spread of the infection. Antigen detection tests are also direct diagnostic methods, with the advantage of obtaining the result in a few minutes and at the very "pointof-care". Furthermore, the simplicity and low cost of these tests allow them to be repeated on successive days in certain clinical settings. The sensitivity of antigen tests is generally lower than that of nucleic acid tests, although their specificity is comparable. Antigenic tests have been shown to be more valid in the days around the onset of symptoms, when the viral load in the nasopharynx is higher. Having a rapid and real-time viral detection assay such as the antigen test has been shown to be more useful to control the spread of the infection than more sensitive tests, but with greater cost and response time, such as in case of molecular tests. The main health institutions such as the WHO, the CDC and the Ministry of Health of the Government of Spain propose the use of antigenic tests in a wide variety of strategies to respond to the pandemic. This document aims to support physicians involved in the care of patients with suspected SC2 infection, in the context of a growing incidence in Spain since September 2020, which already represents the second pandemic wave of COVID-19.

[Utilisation of first-line antibiotics six years after a multifaceted intervention]. / Uso de antibióticos de primera línea 6 años después de una intervención multifacética.

OBJECTIVE: No study has evaluated the impact of a multifaceted intervention on the quality of the antibiotics prescribed more than 5 years later. METHODS: A total of 210 general practitioners (GP) from eight different regions of Spain were asked to participate in two registrations of respiratory tract infections (RTI) in 2008, before, and in 2009, just after a multifaceted intervention including prescriber feedback, clinical guidelines, training sessions focused on appropriate antibiotic prescribing, workshop on rapid tests and provision of these tests in the GP consultation. They were all again invited to participate in a similar registration in 2015. A new group of clinicians from the same areas who had never participated in antimicrobial stewardship courses were also invited to participate and acted as controls. RESULTS: The 121 GPs who continued the study (57.6%) and the 117 control GPs registered 22,407 RTIs. The antibiotic most commonly prescribed was amoxicillin and clavulanic acid, prescribed in 1,801 cases (8.1% of the total), followed by amoxicillin (1,372 prescriptions, 6.2%), being lower among GPs just after the intervention. The third leading antibiotic among GPs just after the intervention was penicillin V (127 cases, 3.3%) whereas macrolides ranked third in the other three groups of GPs. CONCLUSIONS: The use of first-line antibiotic for RTIs wanes over time after an intervention, but their utilisation is still significantly greater among intervened clinicians six years later compared to GPs who have never been exposed to any antimicrobial stewardship programmes.

[Clinical management of patient with benign prostatic hyperplasia in Spain]. / Manejo asistencial del paciente con hiperplasia benigna de próstata en España.

OBJECTIVES: To identify clinical management of benign prostatic hyperplasia (BPH) in Spain and its associated health care resources. MATERIAL AND METHODS: A qualitative cross-sectional study was conducted through telephone interviews to general practitioners (GP) and urologists. Information about diagnosis, pharmacologic treatment and follow-up was collected. Results were clustered according to the key variables considered as drivers of clinical practice patterns: BPH diagnosis, severity classification, treatment initiation and follow up of patients. RESULTS: 153 GP and 154 urologists participated in the study. 7 different clinical patterns were identified in primary care (PC). Resource use during diagnosis is relatively homogeneous, reporting a range of 2.0 to 2.6 visits employed and being the most frequent test performed PSA and urine test. Follow-up is heterogeneous; frequency of follow-up visits oscillates from 3.2 to 7.0 visits/patient/year and type of tests performed is different among patterns and within the same pattern. In Urology, 3 clinical patterns were identified. Resource use is homogeneous in the diagnosis and in the follow-up; urologists employed 2 visits in diagnosis and a range of 2.1 to 3.2 visits/patient/year in the follow-up. The most frequent tests both in diagnosis and follow-up are PSA and digital test. CONCLUSIONS: BPH management shows variability in PC, identifying 7 different clinical practice patterns with different resource use during the follow-up among patterns and within the same pattern. The implementation of clinical guidelines could be justified to reduce heterogeneity.

[Cost-effectiveness of the combination therapy of dutasteride and tamsulosin in the treatment of benign prostatic hyperlasia in Spain]. / Coste-efectividad de la combinación dutasterida y tamsulosina en el tratamiento de la hiperplasia benigna de próstata en España.

OBJECTIVES: to evaluate the incremental cost-effectiveness ratio (ICER) of the combination therapy with dutasteride and tamsulosin (DUT+TAM) as initiation treatment versus the most used drug in Spain, tamsulosin (TAM), in the treatment of moderate to severe benign prostatic hyperplasia (BPH) with risk of progression. METHODS: a semi-Markov model was developed using 4-year and 35-year time horizons and from the Spanish National Healthcare Service perspective. Data were obtained from the CombAT trial. Effectiveness was measured in terms of quality adjusted life years (QALYs). Health care resources were defined by an experts' panel, and unitary costs were obtained from published Spanish sources. Pharmacologic cost is expressed in PTP(WAT); in the case of TAM, the generic price is used, in the case of DUT+TAM the price of a fixed dose combination is used. Costs are expressed in 2010 Euros. RESULTS: combination therapy with DUT+TAM produces an incremental effectiveness of 0.06QALY at year 4 and 0.4QALY at year 35. DUT+TAM represents an incremental cost of € 810.53 at 4 years and € 3,443.62 at 35 years. Therefore, the ICER for DUT+TAM versus TAM is € 14,023.32/QALY at year 4 and € 8,750.15/QALY at year 35. CONCLUSIONS: initiation treatment with DUT+TAM represents a cost-effective treatment versus TAM, the most used treatment in Spain, due to the fact the ICER is below the threshold that usually allows a technology to be considered as cost-effective.

[Referral criteria for benign prostatic hyperplasia in primary care.Sociedad Española de Médicos de Atención Primaria, Sociedad Española de Medicina General, Sociedad Española de Medicina de Familia y Comunitaria, Asociación Española de Urología]. / Criterios de derivación en hiperplasia benigna de próstata para atención primaria. Sociedad Española de Médicos de Atención Primaria, Sociedad Española de Medicina General, Sociedad Española de Medicina de Familia y Comunitaria, y la Asociación Española de Urología.

Benign prostatic hyperplasia (BPH) is a high prevalence condition in men over 50 years that requires continued assistance between primary care and urology. Therefore, consensus around common referral criteria was needed to guide and support both levels. Medical history, symptom assessment with International Prostate Symptom Score (IPSS) questionnaire, digital rectal examination and prostate-specific antigen (PSA) measurement are diagnostic tests available for general practitioners that allow setting a correct BPH diagnose. Patients with an IPSS<8 should be monitored by evaluating them annually. Treatment with alpha-blockers and an evaluation at the first and third month is recommended in patients with an IPSS 8-20 and if the prostate is small, if the prostate size is large treatment with alpha-blockers or 5alpha-reductase inhibitors and evaluation at the third and six month is recommended, and in patients with a large prostate and a PSA >1.5 ng/ ml combined treatment and evaluation at the first and sixth month is recommended. Some clear criteria for referral to urology are established in this document, which help in the management of these patients. Those patients with BPH who do not show any improvement at the third month of treatment with alpha-blockers, or the sixth month with 5alpha-reductase inhibitors, will be referred to urology. Patients will also be referred to urology if they have lower urinary tract symptoms, a pathological finding during rectal examination, IPSS>20, PSA>10 ng/ml or PSA>4 ng/ml and free PSA<20% or if they are <50 years with suspected BHP, or if they have any urological complication.