Letter to the Editor
Debating pharmacological options for dyspnoea relief; the need for full, accurate and balanced critical appraisal of the evidence
Joanna C. Grogono
Corresponding author
Oxford University Hospitals NHS Trust, John Radcliffe Hospital, OX3 9DU, United Kingdom
Kyle T.S. Pattinson
Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, OX3 9DU, United Kingdom
Shakeeb H. Moosavi
Department of Biological and Medical Sciences, Oxford Brookes University, OX3 0BP, United Kingdom
Read
3931
Timeswas read the article
1971
Total PDF
1960
Total HTML
Share statistics
array:23 [ "pii" => "S2531043719301394" "issn" => "25310437" "doi" => "10.1016/j.pulmoe.2019.07.008" "estado" => "S300" "fechaPublicacion" => "2019-11-01" "aid" => "1393" "copyrightAnyo" => "2019" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "cor" "cita" => "Pulmonol. 2019;25:355-6" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 506 "formatos" => array:3 [ "EPUB" => 61 "HTML" => 267 "PDF" => 178 ] ] "itemSiguiente" => array:19 [ "pii" => "S2531043719301667" "issn" => "25310437" "doi" => "10.1016/j.pulmoe.2019.08.002" "estado" => "S300" "fechaPublicacion" => "2019-11-01" "aid" => "1399" "copyright" => "Sociedade Portuguesa de Pneumologia" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "cor" "cita" => "Pulmonol. 2019;25:356-7" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 504 "formatos" => array:3 [ "EPUB" => 68 "HTML" => 261 "PDF" => 175 ] ] "en" => array:9 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Strategies to relieve dyspnoea in patients with advanced chronic respiratory diseases. A narrative review. Authors’ reply" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "356" "paginaFinal" => "357" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Nicolino Ambrosino, Claudio Fracchia" "autores" => array:2 [ 0 => array:2 [ "nombre" => "Nicolino" "apellidos" => "Ambrosino" ] 1 => array:2 [ "nombre" => "Claudio" "apellidos" => "Fracchia" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2531043719301667?idApp=UINPBA00004E" "url" => "/25310437/0000002500000006/v1_201911020923/S2531043719301667/v1_201911020923/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S2531043719301631" "issn" => "25310437" "doi" => "10.1016/j.pulmoe.2019.08.001" "estado" => "S300" "fechaPublicacion" => "2019-11-01" "aid" => "1398" "copyright" => "Sociedade Portuguesa de Pneumologia" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "rev" "cita" => "Pulmonol. 2019;25:348-54" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 941 "formatos" => array:3 [ "EPUB" => 70 "HTML" => 610 "PDF" => 261 ] ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Review</span>" "titulo" => "High flow through nasal cannula in exacerbated COPD patients: a systematic review" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "348" "paginaFinal" => "354" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 951 "Ancho" => 2342 "Tamanyo" => 186144 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Risk of bias graph. The figure illustrates the proportion of studies with each of the judgements (‘Low risk’, ‘High risk’, ‘Unclear risk’ of bias).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "L. Pisani, M. Astuto, I. Prediletto, F. Longhini" "autores" => array:4 [ 0 => array:2 [ "nombre" => "L." "apellidos" => "Pisani" ] 1 => array:2 [ "nombre" => "M." "apellidos" => "Astuto" ] 2 => array:2 [ "nombre" => "I." "apellidos" => "Prediletto" ] 3 => array:2 [ "nombre" => "F." "apellidos" => "Longhini" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2531043719301631?idApp=UINPBA00004E" "url" => "/25310437/0000002500000006/v1_201911020923/S2531043719301631/v1_201911020923/en/main.assets" ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Debating pharmacological options for dyspnoea relief; the need for full, accurate and balanced critical appraisal of the evidence" "tieneTextoCompleto" => true "saludo" => "To the editor," "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "355" "paginaFinal" => "356" ] ] "autores" => array:3 [ 0 => array:4 [ "autoresLista" => "Joanna C. Grogono" "autores" => array:1 [ 0 => array:4 [ "nombre" => "Joanna C." "apellidos" => "Grogono" "email" => array:1 [ 0 => "Joanna.Grogono@ouh.nhs.uk" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Oxford University Hospitals NHS Trust, John Radcliffe Hospital, OX3 9DU, United Kingdom" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] 1 => array:3 [ "autoresLista" => "Kyle T.S. Pattinson" "autores" => array:1 [ 0 => array:3 [ "nombre" => "Kyle T.S." "apellidos" => "Pattinson" "email" => array:1 [ 0 => "kyle.pattinson@nda.ox.ac.uk" ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, OX3 9DU, United Kingdom" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "autoresLista" => "Shakeeb H. Moosavi" "autores" => array:1 [ 0 => array:3 [ "nombre" => "Shakeeb H." "apellidos" => "Moosavi" "email" => array:1 [ 0 => "smoosavi@brookes.ac.uk" ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Department of Biological and Medical Sciences, Oxford Brookes University, OX3 0BP, United Kingdom" "identificador" => "aff0015" ] ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">We read with interest the review on strategies to relieve dyspnoea in patients with advanced chronic respiratory disease by Ambrosino and Fracchia.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Given the clinical need for pharmacological options for dyspnoea relief, we would like to comment on some important aspects that we feel merit further clarification.</p><p id="par0010" class="elsevierStylePara elsevierViewall">The review comments on inhaled furosemide as a potential drug for relieving dyspnoea and refers to our RCT in healthy volunteers<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> which showed significant relief of experimentally-induced air hunger. The review stipulates that this was “<span class="elsevierStyleItalic">a finding not confirmed later even at higher doses</span>.”<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> The comment is misleading, implying that higher-dose studies were completed subsequent to ours and that the findings were incongruous. Our study<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> was published <span class="elsevierStyleItalic">after</span> the higher-dose studies. The controlled delivery of 80<span class="elsevierStyleHsp" style=""></span>mg <span class="elsevierStyleItalic">was</span> associated with greater air hunger relief<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> compared to what we found with uncontrolled delivery of 40mg (mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SE: −17<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>3 versus −11<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>5%VAS). However, the greater relief in the higher-dose study was offset by a larger placebo effect (−13<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>4 versus −2.5<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>4%VAS). The enhanced placebo effect in the higher-dose study can be explained by differences in study design.</p><p id="par0015" class="elsevierStylePara elsevierViewall">While there is high variability in dyspnoea relief in all published studies of inhaled furosemide, there is potential for it to form a viable treatment option for the most unpleasant form of dyspnoea if the sources of variability are unravelled. Potential sources of variability include, i) site of drug deposition in the lungs ii) rate of extinction from the lungs iii) lack of information on the quality of dyspnoea rated and iv) use of a dyspnoea model that is not focussed on ‘air hunger’. More research with inhaled furosemide is justified given that it is safe, inexpensive and underpinned by a defined physiological mechanism of action.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The discussion by Ambrosino and Fracchia on the use of opioids for dyspnoea relief is also misleading and fails to paint a balanced picture. The authors have ignored the opioid crisis that has killed over ¾ million Americans since 1999.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> They have not considered the absence of long-term studies of opioid efficacy or safety.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> In most people, opioid efficacy is high in the short term but diminishes over 6 weeks to 3 months. The resultant dose escalation increases risk of adverse events with no improvement in symptoms.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> We suggest extreme caution is necessary for prescription of opioid medication for breathlessness because, i) opioids increase risk for death in people with lung conditions,<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> ii) people with anxiety/depression are more likely to have diminished opioid response to pain,<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> and breathlessness,<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> but also are more likely to have problems with dependency and failure to wean off opioids.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Finally the author's assertion that "<span class="elsevierStyleItalic">Relief of dyspnoea […] is a human right</span>" echoes sentiments expressed in the mid 1980′s that were used to justify using opioids for all kinds of pain,<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> leading to the opioid crisis we are in today. It is preposterous to portray those who harbour legitimate concerns about opioid safety as human rights violators when the debate is not fuelled by a balanced appraisal of the evidence.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Statement of ethics</span><p id="par0030" class="elsevierStylePara elsevierViewall">The authors have no ethical conflicts to disclose.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Funding</span><p id="par0035" class="elsevierStylePara elsevierViewall">The authors have not received any funding specifically for this correspondence.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Author contributions</span><p id="par0040" class="elsevierStylePara elsevierViewall">All authors contributed equally to this correspondence.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Conflict of interest</span><p id="par0045" class="elsevierStylePara elsevierViewall">KP has acted as a consultant for Nektar Therapeutics. The work for Nektar has no bearing on the contents of this manuscript. KP is named as a co-inventor on a provisional UK patent application titled “Use of cerebral nitric oxide donors in the assessment of the extent of brain dysfunction following injury".</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Statement of ethics" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Funding" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Author contributions" ] 3 => array:2 [ "identificador" => "sec0020" "titulo" => "Conflict of interest" ] 4 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2019-07-02" "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:7 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Strategies to relieve dyspnoea in patients with advanced chronic respiratory diseases. A narrative review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "N. Ambrosino" 1 => "C. Fracchia" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.pulmoe.2019.04.002" "Revista" => array:7 [ "tituloSerie" => "Pulmonology" "fecha" => "2019" "volumen" => "25" "numero" => "5" "paginaInicial" => "289" "paginaFinal" => "298" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31129045" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Inhaled furosemide for relief of air hunger versus sense of breathing effort: a randomized controlled trial" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "J.C. Grogono" 1 => "C. Butler" 2 => "H. Izadi" 3 => "S.H. Moosavi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s12931-018-0886-9" "Revista" => array:6 [ "tituloSerie" => "Respir Res" "fecha" => "2018" "volumen" => "19" "numero" => "1" "paginaInicial" => "181" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30236110" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Aerosol furosemide for dyspnea: high-dose controlled delivery does not improve effectiveness" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "R.B. Banzett" 1 => "R.M. Schwartzstein" 2 => "R.W. Lansing" 3 => "C.R. O’Donnell" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.resp.2017.08.010" "Revista" => array:6 [ "tituloSerie" => "Respir Physiol Neurobiol" "fecha" => "2018" "volumen" => "247" "paginaInicial" => "24" "paginaFinal" => "30" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28843675" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prevention of Opioid Overdose" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "K.M. Babu" 1 => "J. Brent" 2 => "D.N. Juurlink" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMra1807054" "Revista" => array:7 [ "tituloSerie" => "N Engl J Med" "fecha" => "2019" "volumen" => "380" "numero" => "23" "paginaInicial" => "2246" "paginaFinal" => "2255" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31167053" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Adverse respiratory effects of opioids for chronic breathlessness: learning lessons from chronic pain" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "K.T.S. Pattinson" 1 => "M.J. Rowland" 2 => "A.H. Nickol" 3 => "J. Quinlan" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Eur Respir J" "fecha" => "2018" "volumen" => "51" "numero" => "3" ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Opioids for breathlessness: psychological and neural factors influencing response variability" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "S.J. Abdallah" 1 => "O.K. Faull" 2 => "V. Wanigasekera" 3 => "S.L. Finnegan" 4 => "D. Jensen" 5 => "K. Pattinson" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1183/13993003.00275-2019" "Revista" => array:3 [ "tituloSerie" => "Eur Respir J" "fecha" => "2019" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29025888" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Chronic use of opioid analgesics in non-malignant pain: report of 38 cases" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "R.K. Portenoy" 1 => "K.M. Foley" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/0304-3959(86)90091-6" "Revista" => array:7 [ "tituloSerie" => "Pain" "fecha" => "1986" "volumen" => "25" "numero" => "2" "paginaInicial" => "171" "paginaFinal" => "186" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2873550" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/25310437/0000002500000006/v1_201911020923/S2531043719301394/v1_201911020923/en/main.assets" "Apartado" => array:4 [ "identificador" => "72880" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letters to the Editor" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/25310437/0000002500000006/v1_201911020923/S2531043719301394/v1_201911020923/en/main.pdf?idApp=UINPBA00004E&text.app=https://journalpulmonology.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2531043719301394?idApp=UINPBA00004E" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 5 | 5 | 10 |
| 2024 October | 20 | 27 | 47 |
| 2024 September | 30 | 20 | 50 |
| 2024 August | 36 | 37 | 73 |
| 2024 July | 29 | 26 | 55 |
| 2024 June | 35 | 32 | 67 |
| 2024 May | 34 | 31 | 65 |
| 2024 April | 31 | 39 | 70 |
| 2024 March | 34 | 23 | 57 |
| 2024 February | 31 | 29 | 60 |
| 2024 January | 36 | 25 | 61 |
| 2023 December | 20 | 20 | 40 |
| 2023 November | 37 | 40 | 77 |
| 2023 October | 21 | 28 | 49 |
| 2023 September | 31 | 38 | 69 |
| 2023 August | 18 | 19 | 37 |
| 2023 July | 23 | 23 | 46 |
| 2023 June | 14 | 16 | 30 |
| 2023 May | 30 | 36 | 66 |
| 2023 April | 17 | 14 | 31 |
| 2023 March | 23 | 24 | 47 |
| 2023 February | 26 | 15 | 41 |
| 2023 January | 25 | 18 | 43 |
| 2022 December | 34 | 23 | 57 |
| 2022 November | 32 | 36 | 68 |
| 2022 October | 38 | 40 | 78 |
| 2022 September | 22 | 44 | 66 |
| 2022 August | 20 | 30 | 50 |
| 2022 July | 26 | 55 | 81 |
| 2022 June | 19 | 28 | 47 |
| 2022 May | 28 | 33 | 61 |
| 2022 April | 23 | 34 | 57 |
| 2022 March | 29 | 43 | 72 |
| 2022 February | 24 | 43 | 67 |
| 2022 January | 31 | 40 | 71 |
| 2021 December | 29 | 35 | 64 |
| 2021 November | 29 | 41 | 70 |
| 2021 October | 40 | 62 | 102 |
| 2021 September | 20 | 36 | 56 |
| 2021 August | 19 | 28 | 47 |
| 2021 July | 25 | 21 | 46 |
| 2021 June | 39 | 59 | 98 |
| 2021 May | 32 | 50 | 82 |
| 2021 April | 108 | 102 | 210 |
| 2021 March | 66 | 35 | 101 |
| 2021 February | 20 | 30 | 50 |
| 2021 January | 23 | 19 | 42 |
| 2020 December | 23 | 21 | 44 |
| 2020 November | 22 | 24 | 46 |
| 2020 October | 16 | 23 | 39 |
| 2020 September | 38 | 34 | 72 |
| 2020 August | 29 | 31 | 60 |
| 2020 July | 45 | 18 | 63 |
| 2020 June | 33 | 22 | 55 |
| 2020 May | 31 | 19 | 50 |
| 2020 April | 34 | 18 | 52 |
| 2020 March | 23 | 17 | 40 |
| 2020 February | 37 | 29 | 66 |
| 2020 January | 62 | 49 | 111 |
| 2019 December | 54 | 30 | 84 |
| 2019 November | 81 | 53 | 134 |
| 2019 October | 27 | 16 | 43 |
| 2019 September | 23 | 15 | 38 |
Show all
