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Rombo, Lars
Publications (10 of 10) Show all publications
Dahal, P., Simpson, J. A., Abdulla, S., Achan, J., Adam, I., Agarwal, A., . . . Stepniewska, K. (2019). Competing risk events in antimalarial drug trials in uncomplicated Plasmodium falciparum malaria: a WorldWide Antimalarial Resistance Network individual participant data meta-analysis. Malaria Journal, 18, Article ID 225.
Open this publication in new window or tab >>Competing risk events in antimalarial drug trials in uncomplicated Plasmodium falciparum malaria: a WorldWide Antimalarial Resistance Network individual participant data meta-analysis
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2019 (English)In: Malaria Journal, ISSN 1475-2875, E-ISSN 1475-2875, Vol. 18, article id 225Article in journal (Refereed) Published
Abstract [en]

Background: Therapeutic efficacy studies in uncomplicated Plasmodium falciparum malaria are confounded by new infections, which constitute competing risk events since they can potentially preclude/pre-empt the detection of subsequent recrudescence of persistent, sub-microscopic primary infections.

Methods: Antimalarial studies typically report the risk of recrudescence derived using the Kaplan-Meier (K-M) method, which considers new infections acquired during the follow-up period as censored. Cumulative Incidence Function (CIF) provides an alternative approach for handling new infections, which accounts for them as a competing risk event. The complement of the estimate derived using the K-M method (1 minus K-M), and the CIF were used to derive the risk of recrudescence at the end of the follow-up period using data from studies collated in the WorldWide Antimalarial Resistance Network data repository. Absolute differences in the failure estimates derived using these two methods were quantified. In comparative studies, the equality of two K-M curves was assessed using the log-rank test, and the equality of CIFs using Gray's k-sample test (both at 5% level of significance). Two different regression modelling strategies for recrudescence were considered: cause-specific Cox model and Fine and Gray's sub-distributional hazard model.

Results: Data were available from 92 studies (233 treatment arms, 31,379 patients) conducted between 1996 and 2014. At the end of follow-up, the median absolute overestimation in the estimated risk of cumulative recrudescence by using 1 minus K-M approach was 0.04% (interquartile range (IQR): 0.00-0.27%, Range: 0.00-3.60%). The overestimation was correlated positively with the proportion of patients with recrudescence [Pearson's correlation coefficient (rho): 0.38, 95% Confidence Interval (CI) 0.30-0.46] or new infection [rho: 0.43; 95% CI 0.35-0.54]. In three study arms, the point estimates of failure were greater than 10% (the WHO threshold for withdrawing antimalarials) when the K-M method was used, but remained below 10% when using the CIF approach, but the 95% confidence interval included this threshold.

Conclusions: The 1 minus K-M method resulted in a marginal overestimation of recrudescence that became increasingly pronounced as antimalarial efficacy declined, particularly when the observed proportion of new infection was high. The CIF approach provides an alternative approach for derivation of failure estimates in antimalarial trials, particularly in high transmission settings.

Place, publisher, year, edition, pages
BMC, 2019
Keywords
Plasmodium falciparum, Treatment efficacy study, Competing risk event
National Category
Infectious Medicine
Identifiers
urn:nbn:se:uu:diva-391014 (URN)10.1186/s12936-019-2837-4 (DOI)000474589900001 ()31277713 (PubMedID)
Funder
Wellcome trust, 200909
Available from: 2019-08-21 Created: 2019-08-21 Last updated: 2019-08-21Bibliographically approved
Rosdahl, A., Herzog, C., Frösner, G., Norén, T., Rombo, L. & Askling, H. H. (2019). Corrigendum to " An extra priming dose of hepatitis A vaccine to adult patients with rheumatoid arthritis and drug induced immunosuppression - A prospective, open-label, multi-center study" [Trav. Med. Infect. Dis. 21, January-February 2018, 43-50].. Travel Medicine and Infectious Disease, 27, 115-115
Open this publication in new window or tab >>Corrigendum to " An extra priming dose of hepatitis A vaccine to adult patients with rheumatoid arthritis and drug induced immunosuppression - A prospective, open-label, multi-center study" [Trav. Med. Infect. Dis. 21, January-February 2018, 43-50].
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2019 (English)In: Travel Medicine and Infectious Disease, ISSN 1477-8939, E-ISSN 1873-0442, Vol. 27, p. 115-115Article in journal (Refereed) Published
National Category
Infectious Medicine
Identifiers
urn:nbn:se:uu:diva-374019 (URN)10.1016/j.tmaid.2018.09.008 (DOI)000457729300020 ()30292695 (PubMedID)
Available from: 2019-01-17 Created: 2019-01-17 Last updated: 2019-03-01Bibliographically approved
Wilkinson, T. M. A., Schembri, S., Brightling, C., Bakerly, N. D., Lewis, K., MacNee, W., . . . Arora, A. K. (2019). Non-typeable Haemophilus influenzae protein vaccine in adults with COPD: A phase 2 clinical trial. Vaccine, 37(41), 6102-6111
Open this publication in new window or tab >>Non-typeable Haemophilus influenzae protein vaccine in adults with COPD: A phase 2 clinical trial
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2019 (English)In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 37, no 41, p. 6102-6111Article in journal (Refereed) Published
Abstract [en]

Loss of airway microbial diversity is associated with non-typeable Haemophilus influenzae (NTHi) infection and increased risk of exacerbation in chronic obstructive pulmonary disease (COPD). We assessed the safety and immunogenicity of an investigational vaccine containing NTHi antigens, recombinant protein D (PD) and combined protein E and Pilin A (PE-PilA), and AS01 adjuvant in adults with moderate/-severe COPD and prior exacerbations. In this phase 2, observer-blind, controlled trial (NCT02075541), 145 COPD patients aged 40-80 years randomly (1:1) received two doses of NTHi vaccine or placebo 60 days apart, on top of standard care. Reactogenicity in the 7-day post-vaccination period was higher following NTHi vaccine than placebo. Most solicited adverse events (AEs) were mild/moderate. At least one unsolicited AE was reported during the 30-day post-vaccination period by 54.8% of NTHi vaccine and 51.4% of placebo recipients. One serious AE (placebo group) was assessed by the investigator as vaccine-related. Anti-PD, anti-PE and anti-PiIA geometric mean antibody concentrations increased up to 30 days after each NTHi vaccine dose, waned thereafter, but remained higher than baseline (non-overlapping confidence intervals) up to 13 months post-dose 2. The frequency of specific CD4(+) T cells increased following two doses of NTHi vaccine and remained higher than baseline. Exploratory analysis showed a statistically non-significant lower yearly rate of moderate/severe exacerbations in the NTHi vaccine group than following placebo (1.49 versus 1.73) in the one-year period post-dose 2, with estimated vaccine efficacy of 13.3% (95% confidence interval -24.2 to 39.5; p = 0.44). The NTHi vaccine had an acceptable safety and reactogenicity profile and good immunogenicity in adults with COPD.

Keywords
Non-typeable Haemophilus influenzae, COPD, Exacerbation, Vaccine, Safety, Immunogenicity
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:uu:diva-395796 (URN)10.1016/j.vaccine.2019.07.100 (DOI)000487568800012 ()31447126 (PubMedID)
Available from: 2019-10-25 Created: 2019-10-25 Last updated: 2019-10-25Bibliographically approved
Lopez-Fauqued, M., Campora, L., Delannois, F., El Idrissi, M., Oostvogels, L., De Looze, F. J., . . . Zahaf, T. (2019). Safety profile of the adjuvanted recombinant zoster vaccine: Pooled analysis of two large randomised phase 3 trials. Vaccine, 37(18), 2482-2493
Open this publication in new window or tab >>Safety profile of the adjuvanted recombinant zoster vaccine: Pooled analysis of two large randomised phase 3 trials
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2019 (English)In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 37, no 18, p. 2482-2493Article in journal (Refereed) Published
Abstract [en]

Background: The ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229) phase 3 clinical trials showed that the adjuvanted recombinant zoster vaccine (RZV) was >= 90% efficacious in preventing herpes zoster in adults. Here we present a comprehensive overview of the safety data from these studies.

Methods: Adults aged >= 50 (ZOE-50) and >= 70 (ZOE-70) years were randomly vaccinated with RZV or placebo. Safety analyses were performed on the pooled total vaccinated cohort, consisting of participants receiving at least one dose of RZV or placebo. Solicited and unsolicited adverse events (AEs) were collected for 7 and 30 days after each vaccination, respectively. Serious AEs (SAEs) were collected from the first vaccination until 12 months post-last dose. Fatal AEs, vaccination-related SAEs, and potential immune-mediated diseases (pIMDs) were collected during the entire study period.

Results: Safety was evaluated in 14,645 RZV and 14,660 placebo recipients. More RZV than placebo recipients reported unsolicited AEs (50.5% versus 32.0%); the difference was driven by transient injection site and solicited systemic reactions that were generally seen in the first week post-vaccination. The occurrence of overall SAEs (RZV: 10.1%; Placebo: 10.4%), fatal AEs (RZV: 4.3%; Placebo: 4.6%), and pIMDs (RZV: 1.2%; Placebo: 1.4%) was balanced between groups. The occurrence of possible exacerbations of pIMDs was rare and similar between groups. Overall, except for the expected local and systemic symptoms, the safety results were comparable between the RZV and Placebo groups irrespective of participant age, gender, or race.

Conclusions: No safety concerns arose, supporting the favorable benefit-risk profile of RZV. 

Place, publisher, year, edition, pages
ELSEVIER SCI LTD, 2019
Keywords
Varicella-zoster virus, Vaccine, Safety, Reactogenicity
National Category
General Practice
Identifiers
urn:nbn:se:uu:diva-387212 (URN)10.1016/j.vaccine.2019.03.043 (DOI)000466622500009 ()30935742 (PubMedID)
Available from: 2019-06-25 Created: 2019-06-25 Last updated: 2019-06-25Bibliographically approved
Rosdahl, A., Herzog, C., Frösner, G., Norén, T., Rombo, L. & Askling, H. H. (2018). An extra priming dose of hepatitis A vaccine to adult patients with rheumatoid arthritis and drug induced immunosuppression: A prospective, open-label, multi-center study. Travel Medicine and Infectious Disease, 21, 43-50
Open this publication in new window or tab >>An extra priming dose of hepatitis A vaccine to adult patients with rheumatoid arthritis and drug induced immunosuppression: A prospective, open-label, multi-center study
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2018 (English)In: Travel Medicine and Infectious Disease, ISSN 1477-8939, E-ISSN 1873-0442, Vol. 21, p. 43-50Article in journal (Refereed) Published
Abstract [en]

BACKGROUND:

Previous studies have indicated that a pre-travel single dose of hepatitis A vaccine is not sufficient as protection against hepatitis A in immunocompromised travelers. We evaluated if an extra dose of hepatitis A vaccine given shortly prior to traveling ensures seroconversion.

METHOD:

Patients with rheumatoid arthritis (n = 69, median age = 55 years) treated with Tumor Necrosis Factor inhibitor(TNFi) and/or Methotrexate (MTX) were immunized with two doses of hepatitis A vaccine, either as double dose or four weeks apart, followed by a booster dose at six months. Furthermore, 48 healthy individuals, median age = 60 years were immunized with two doses, six months apart. Anti-hepatitis A antibodies were measured at 0, 1, 2, 6, 7 and 12 months.

RESULTS:

Two months after the initial vaccination, 84% of the RA patients had protective antibodies, compared to 85% of the healthy individuals. There was no significant difference between the two vaccine schedules. At twelve months, 99% of RA patients and 100% of healthy individuals had seroprotective antibodies.

CONCLUSION:

An extra priming dos of hepatitis A vaccine prior to traveling offered an acceptable protection in individuals treated with TNFi and/or MTX. This constitutes an attractive pre-travel solution to this vulnerable group of patients.

Keywords
Hepatitis A, Immunosuppression, Methotrexate, Rheumatoid arthritis, TNF-Inhibitors, Vaccine
National Category
Infectious Medicine
Identifiers
urn:nbn:se:uu:diva-342510 (URN)10.1016/j.tmaid.2017.12.004 (DOI)000426614600006 ()29229311 (PubMedID)
Available from: 2018-02-21 Created: 2018-02-21 Last updated: 2018-05-16Bibliographically approved
Leung, T. F., Liu, A.-Y. P., Lim, F. S., Thollot, F., Oh, H. M., Lee, B. W., . . . Struyf, F. (2018). Comparative immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and 4vHPV vaccine administered according to two- or three-dose schedules in girls aged 9-14 years: Results to month 36 from a randomized trial. Vaccine, 36(1), 98-106
Open this publication in new window or tab >>Comparative immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and 4vHPV vaccine administered according to two- or three-dose schedules in girls aged 9-14 years: Results to month 36 from a randomized trial
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2018 (English)In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 36, no 1, p. 98-106Article in journal (Refereed) Published
Abstract [en]

This observer-blind study (clinicaltrials.gov NCT01462357) compared the immunogenicity and safety of two doses (2D) of the HPV-16/18 AS04-adjuvanted vaccine (2D of AS04-HPV-16/18) vs. two or three doses of the 4vHPV vaccine [2D or 3D of 4vHPV] in 1075 healthy girls aged 9-14 years. Girls were randomized (1:1:1) to receive 2D of AS04-HPV-16/18 at months (M) 0, 6 (N = 359), 2D of 4vHPV at MO, 6 (N = 358) or 3D of 4vHPV at MO, 2, 6 (N = 358). 351, 339 and 346 girls, respectively, returned for the concluding visit at M36. Superiority was demonstrated at M7 and M12; comparison of the immune response to both vaccine antigens was made between 2D of AS04-HPV-16/18 and 2D or 3D of 4vHPV at subsequent time points in the according-to-protocol immunogenicity cohort (ATP-I; N = 958 at M36) and the total vaccinated cohort (TVC: N = 1036 at M36). HPV-16/18-specific T-cell- and B-cell-mediated immune responses and safety were also investigated. At M36, anti-HPV-16/18 ELISA responses in the 2D AS04-HPV-16/18 group remained superior to those of the 2D and 3D 4vHPV groups. In the M36 TVC, geometric mean titers were 2.78-fold (HPV-16) and 6.84-fold (HPV-18) higher for 2D of AS04-HPV-16/18 vs. 2D of 4vHPV and 2.3-fold (HPV-16) and 4.14-fold (HPV-18) higher vs. 3D of 4vHPV. Results were confirmed by vaccine pseudovirion-based neutralisation assay. Numbers of circulating CD4(+) T cells and B cells appeared similar across groups. Safety was in line with the known safety profiles of both vaccines. In conclusion, superior HPV-16/18 antibody responses were elicited by 2D of the AS04-HPV-16/18 compared with 2D or 3D of the 4vHPV vaccine in girls aged 9-14 years.

Place, publisher, year, edition, pages
ELSEVIER SCI LTD, 2018
Keywords
Human papillomavirus vaccines, Administration schedule, Female adolescents, Immunogenicity, Safety
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-341304 (URN)10.1016/j.vaccine.2017.11.034 (DOI)000419411400015 ()29174109 (PubMedID)
Funder
GlaxoSmithKline (GSK)
Available from: 2018-02-12 Created: 2018-02-12 Last updated: 2018-02-12Bibliographically approved
Albinsson, B., Vene, S., Rombo, L., Blomberg, J., Lundkvist, Å. & Rönnberg, B. (2018). Distinction between serological responses following tick-borne encephalitis virus (TBEV) infection vs vaccination, Sweden 2017. Eurosurveillance, 23(3), 2-7, Article ID 17-00838.
Open this publication in new window or tab >>Distinction between serological responses following tick-borne encephalitis virus (TBEV) infection vs vaccination, Sweden 2017
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2018 (English)In: Eurosurveillance, ISSN 1025-496X, E-ISSN 1560-7917, Vol. 23, no 3, p. 2-7, article id 17-00838Article in journal (Refereed) Published
Abstract [en]

Tick-borne encephalitis virus (TBEV) is an important European vaccine-preventable pathogen. Discrimination of vaccine-induced antibodies from those elicited by infection is important. We studied anti-TBEV IgM/IgG responses, including avidity and neutralisation, by multiplex serology in 50 TBEV patients and 50 TBEV vaccinees. Infection induced antibodies reactive to both whole virus (WV) and non-structural protein 1 (NS1) in 48 clinical cases, whereas 47 TBEV vaccinees had WV, but not NS1 antibodies, enabling efficient discrimination of infection/vaccination.

National Category
Infectious Medicine
Identifiers
urn:nbn:se:uu:diva-343857 (URN)10.2807/1560-7917.ES.2018.23.3.17-00838 (DOI)000423449200001 ()
Available from: 2018-03-02 Created: 2018-03-02 Last updated: 2018-03-02Bibliographically approved
Wilkinson, T., Schembri, S., Brightling, C., Bakerly, N. D., Macnee, W., Rombo, L., . . . Arora, A. K. (2018). Late Breaking Abstract - Safety and immunogenicity of non-typeable H. influenzae (NTHi) adjuvanted vaccine in older adults with chronic obstructive pulmonary disease (COPD). Paper presented at 28th International Congress of the European-Respiratory-Society (ERS), SEP 15-19, 2018, Paris, FRANCE. European Respiratory Journal, 52
Open this publication in new window or tab >>Late Breaking Abstract - Safety and immunogenicity of non-typeable H. influenzae (NTHi) adjuvanted vaccine in older adults with chronic obstructive pulmonary disease (COPD)
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2018 (English)In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 52Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
EUROPEAN RESPIRATORY SOC JOURNALS LTD, 2018
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:uu:diva-375823 (URN)10.1183/13993003.congress-2018.PA4089 (DOI)000455567105229 ()
Conference
28th International Congress of the European-Respiratory-Society (ERS), SEP 15-19, 2018, Paris, FRANCE
Funder
GlaxoSmithKline (GSK)
Available from: 2019-02-04 Created: 2019-02-04 Last updated: 2019-02-04Bibliographically approved
Schwarz, T. F., Volpe, S., Catteau, G., Chlibek, R., David, M. P., Richardus, J. H., . . . Bastidas, A. (2018). Persistence of immune response to an adjuvanted varicella-zoster virus subunit vaccine for up to year nine in older adults. Human Vaccines & Immunotherapeutics, 14(6), 1370-1377
Open this publication in new window or tab >>Persistence of immune response to an adjuvanted varicella-zoster virus subunit vaccine for up to year nine in older adults
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2018 (English)In: Human Vaccines & Immunotherapeutics, ISSN 2164-5515, E-ISSN 2164-554X, Vol. 14, no 6, p. 1370-1377Article in journal (Refereed) Published
Abstract [en]

Background: In adults aged 60years, two doses of the herpes zoster subunit vaccine (HZ/su; 50 mu g varicella-zoster virus glycoprotein E [gE] and AS01(B) Adjuvant System) elicited humoral and cell-mediated immune responses persisting for at least six years. We assessed immunogenicity nine years post-initial vaccination.Methods: This open extension study (NCT02735915) followed 70 participants who received two HZ/su doses in the initial trial (NCT00434577). Blood samples to assess the cellular (intracellular cytokine staining) and humoral (ELISA) immunity were taken at year nine post-initial vaccination.Results: Participants' mean age at dose 1 was 72.3years. The fold increases over pre-vaccination in the mean frequency of gE-specific CD4+ T-cells expressing 2 activation markers plateaued from year four post-dose 1 until year nine. Anti-gE antibody geometric mean concentrations plateaued and remained above pre-vaccination levels from year four onwards. Immunogenicity at year nine was similar across age strata (60-69, 70years) and confirmed statistical prediction model results using data for up to year six. Further modeling using all data up to year nine predicted immune responses would remain above the pre-vaccination level up to year 15.Conclusion: In adults aged 60years, HZ/su-induced immunogenicity remained above pre-vaccination levels for at least nine years post-initial vaccination.Summary: After vaccination with HZ/su, both cell mediated and humoral immunity remained above pre-vaccination levels up to year 9 regardless of age group. Immune responses are predicted to remain above baseline up to 15years post initial vaccination.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS INC, 2018
Keywords
herpes zoster (shingles) vaccine, herpes zoster, immunity, persistence, prediction modeling, prevention, subunit gE vaccine, varicella-zoster virus
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-361012 (URN)10.1080/21645515.2018.1442162 (DOI)000436838100019 ()29461919 (PubMedID)
Available from: 2018-09-20 Created: 2018-09-20 Last updated: 2019-02-01Bibliographically approved
Heywood, A. E., Nothdurft, H., Tessier, D., Moodley, M., Rombo, L., Marano, C. & De Moerlooze, L. (2017). Pre-travel advice, attitudes and hepatitis A and B vaccination rates among travellers from seven countries. Journal of Travel Medicine, 24(1), Article ID taw069.
Open this publication in new window or tab >>Pre-travel advice, attitudes and hepatitis A and B vaccination rates among travellers from seven countries
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2017 (English)In: Journal of Travel Medicine, ISSN 1195-1982, E-ISSN 1708-8305, Vol. 24, no 1, article id taw069Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Knowledge about the travel-associated risks of hepatitis A and B, and the extent of pre-travel health-advice being sought may vary between countries.

METHODS: An online survey was undertaken to assess the awareness, advice-seeking behaviour, rates of vaccination against hepatitis A and B and adherence rates in Australia, Finland, Germany, Norway, Sweden, the UK and Canada between August and October 2014. Individuals aged 18-65 years were screened for eligibility based on: travel to hepatitis A and B endemic countries within the past 3 years, awareness of hepatitis A, and/or combined hepatitis A&B vaccines; awareness of their self-reported vaccination status and if vaccinated, vaccination within the last 3 years. Awareness and receipt of the vaccines, sources of advice, reasons for non-vaccination, adherence to recommended doses and the value of immunization reminders were analysed.

RESULTS: Of 27 386 screened travellers, 19 817 (72%) were aware of monovalent hepatitis A or combined A&B vaccines. Of these 13 857 (70%) had sought advice from a healthcare provider (HCP) regarding combined hepatitis A&B or monovalent hepatitis A vaccination, and 9328 (67%) were vaccinated. Of 5225 individuals eligible for the main survey (recently vaccinated = 3576; unvaccinated = 1649), 27% (841/3111) and 37% (174/465) of vaccinated travellers had adhered to the 3-dose combined hepatitis A&B or 2-dose monovalent hepatitis A vaccination schedules, respectively. Of travellers partially vaccinated against combined hepatitis A&B or hepatitis A, 84% and 61%, respectively, believed that they had received the recommended number of doses.

CONCLUSIONS: HCPs remain the main source of pre-travel health advice. The majority of travellers who received monovalent hepatitis A or combined hepatitis A&B vaccines did not complete the recommended course. These findings highlight the need for further training of HCPs and the provision of reminder services to improve traveller awareness and adherence to vaccination schedules.

Place, publisher, year, edition, pages
Oxford University Press, 2017
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:uu:diva-311902 (URN)10.1093/jtm/taw069 (DOI)000402823100004 ()27738112 (PubMedID)
Funder
GlaxoSmithKline (GSK)
Available from: 2017-01-03 Created: 2017-01-03 Last updated: 2019-02-27Bibliographically approved
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