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  1. Dureja S, McDonnell M, Van Genechten D, Bouvier C, Kolarova T, O'Toole D, et al.
    J Neuroendocrinol, 2023 Jun;35(6):e13310.
    PMID: 37351944 DOI: 10.1111/jne.13310
    SCAN, an online survey, measured access to diagnosis, treatments and monitoring of neuroendocrine tumor (NET) patients globally. Between September and November 2019, NET patients and healthcare professionals (HCPs) completed an online, semi-standardized survey with 54 patient questions and 33 HCP questions. A total of 2359 patients with NETs and 436 HCPs responded. Misdiagnosis was common (44% [1043/2359]). Mean time to diagnosis was 4.8 years (standard deviation [SD], 6.2). Compared with global figures (60% [1407/2359]), the availability of 68 Ga-DOTA positron emission tomography (PET)/computed tomography (CT) was significantly lower in Asia (45% [126/280]) and higher in Oceania (86% [171/200]). HCPs reported that 68 Ga-DOTA PET/CT was free/affordable to fewer patients in Emerging and Developing Economies (EDE) than Advanced Economies (AE; 17% [26/150] and 59% [84/142], respectively). Compared with global data (52% [1234/2359]), patient-reported availability of peptide receptor radionuclide therapy (PRRT) was significantly lower in Asia (31% [88/280]) and higher in Oceania (61% [122/200]). Significant differences were observed in average annual NET specialist costs between AE and EDE ($1081 and $2915, respectively). Compared with AE, patients in EDE traveled further for NET specialists (1032 [SD, 1578] and 181 [SD, 496] km, respectively). Patients and HCPs both recommended referral to HCPs that were more knowledgeable in the field of NETs and had better access to NET experts/specialist centers. National care pathways, enhancing HCP NET knowledge and ensuring effective diagnostics and access to appropriate treatments are crucial to improving patient survival and NET care worldwide.
  2. Bryant JM, Harris SR, Parkhill J, Dawson R, Diacon AH, van Helden P, et al.
    Lancet Respir Med, 2013 Dec;1(10):786-92.
    PMID: 24461758 DOI: 10.1016/S2213-2600(13)70231-5
    BACKGROUND: Recurrence of tuberculosis after treatment makes management difficult and is a key factor for determining treatment efficacy. Two processes can cause recurrence: relapse of the primary infection or re-infection with an exogenous strain. Although re-infection can and does occur, its importance to tuberculosis epidemiology and its biological basis is still debated. We used whole-genome sequencing-which is more accurate than conventional typing used to date-to assess the frequency of recurrence and to gain insight into the biological basis of re-infection.

    METHODS: We assessed patients from the REMoxTB trial-a randomised controlled trial of tuberculosis treatment that enrolled previously untreated participants with Mycobacterium tuberculosis infection from Malaysia, South Africa, and Thailand. We did whole-genome sequencing and mycobacterial interspersed repetitive unit-variable number of tandem repeat (MIRU-VNTR) typing of pairs of isolates taken by sputum sampling: one from before treatment and another from either the end of failed treatment at 17 weeks or later or from a recurrent infection. We compared the number and location of SNPs between isolates collected at baseline and recurrence.

    FINDINGS: We assessed 47 pairs of isolates. Whole-genome sequencing identified 33 cases with little genetic distance (0-6 SNPs) between strains, deemed relapses, and three cases for which the genetic distance ranged from 1306 to 1419 SNPs, deemed re-infections. Six cases of relapse and six cases of mixed infection were classified differently by whole-genome sequencing and MIRU-VNTR. We detected five single positive isolates (positive culture followed by at least two negative cultures) without clinical evidence of disease.

    INTERPRETATION: Whole-genome sequencing enables the differentiation of relapse and re-infection cases with greater resolution than do genotyping methods used at present, such as MIRU-VNTR, and provides insights into the biology of recurrence. The additional clarity provided by whole-genome sequencing might have a role in defining endpoints for clinical trials.

    FUNDING: Wellcome Trust, European Union, Medical Research Council, Global Alliance for TB Drug Development, European and Developing Country Clinical Trials Partnership.

  3. Tweed CD, Wills GH, Crook AM, Amukoye E, Balanag V, Ban AYL, et al.
    Int J Tuberc Lung Dis, 2021 Apr 01;25(4):305-314.
    PMID: 33762075 DOI: 10.5588/ijtld.20.0513
    BACKGROUND: Treatment for TB is lengthy and toxic, and new regimens are needed.METHODS: Participants with pulmonary drug-susceptible TB (DS-TB) were randomised to receive: 200 mg pretomanid (Pa, PMD) daily, 400 mg moxifloxacin (M) and 1500 mg pyrazinamide (Z) for 6 months (6Pa200MZ) or 4 months (4Pa200MZ); 100 mg pretomanid daily for 4 months in the same combination (4Pa100MZ); or standard DS-TB treatment for 6 months. The primary outcome was treatment failure or relapse at 12 months post-randomisation. The non-inferiority margin for between-group differences was 12.0%. Recruitment was paused following three deaths and not resumed.RESULTS: Respectively 4/47 (8.5%), 11/57 (19.3%), 14/52 (26.9%) and 1/53 (1.9%) DS-TB outcomes were unfavourable in patients on 6Pa200MZ, 4Pa200MZ, 4Pa100MZ and controls. There was a 6.6% (95% CI -2.2% to 15.4%) difference per protocol and 9.9% (95%CI -4.1% to 23.9%) modified intention-to-treat difference in unfavourable responses between the control and 6Pa200MZ arms. Grade 3+ adverse events affected 68/203 (33.5%) receiving experimental regimens, and 19/68 (27.9%) on control. Ten of 203 (4.9%) participants on experimental arms and 2/68 (2.9%) controls died.CONCLUSION: PaMZ regimens did not achieve non-inferiority in this under-powered trial. An ongoing evaluation of PMD remains a priority.
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