Rapid socio-economic growth accelerates urbanization in Indonesia, which changes many aspect of human lives, and potentially affect disease prevalence and outcome. This thesis aims to investigate... Show moreRapid socio-economic growth accelerates urbanization in Indonesia, which changes many aspect of human lives, and potentially affect disease prevalence and outcome. This thesis aims to investigate the impacts of urbanization on human health, especially metabolic health and allergic disease, by incorporating many aspects of scientific investigation. Our cluster-randomized-controlled trial showed that, helminth infection, a characteristic feature of rural areas, and anthelmintic treatment, could significantly affect metabolic profiles and hormones. Thus, the ongoing deworming program in Indonesia require in parallel, monitoring of the metabolic health. Additionally, based on our prospective cohort study and analysis on a large scale nationally representative data, although Indonesian rural populations have relatively better metabolic profiles compared to urban, lifelong residence in rural areas does not protect their community members from adverse metabolic changes due to urbanization. Next, we observed that majority of individuals with diabetes in Indonesia were undiagnosed and untreated, especially in rural populations, which warrants extensive action plan from all related stakeholders. Lastly, high-dimensional data analyses on the systemic and nasal mucosal immune profiles revealed a stronger inflammatory immune responses in the nasal mucosal of Indonesian urban young adults with allergic rhinitis compared to their rural counterparts. Show less
Trigt, V.R. van; Pelsma, I.C.M.; Kroon, H.M.; Pereira, A.M.; Meulen, C. van der; Kloppenburg, M.; ... ; Claessen, K.M.J.A. 2021
Purpose Pain is a common symptom of acromegaly, impairing health-related quality of life (HR-QoL) significantly despite long-term disease remission. Neuropathic-like pain (NP-like) symptoms are... Show morePurpose Pain is a common symptom of acromegaly, impairing health-related quality of life (HR-QoL) significantly despite long-term disease remission. Neuropathic-like pain (NP-like) symptoms are invalidating, with great impact on HR-QoL. Studies characterizing or investigating the etiology of pain in acromegaly are scarce. Therefore, we aimed to assess NP-like symptoms in a cohort of controlled acromegaly patients. Methods Forty-four long-term controlled acromegaly patients (aged 62.6 +/- 12.6 years; 56.8% female) were included in this cross-sectional study. NP-like symptoms were assessed using the validated painDETECT questionnaire. Patients were divided in three probability-based NP-like symptoms categories based on the total score (range 0-35): unlikely (<= 12), indeterminate (13-18) and likely (>= 19). HR-QoL (physical component score (PCS), and mental component score (MCS)), and self-reported pain were assessed using Short Form-36 (SF-36). Potential risk factors were determined using linear regression analyses. Results Self-reported pain was reported by 35 patients (79.5%). Likely NP-like symptoms were present in 4/44 patients (9.1%), and indeterminate NP-like symptoms in 6/44 patients (13.6%). All patients with likely NP-like symptoms were female. Higher painDETECT scores were negatively associated with HR-QoL (PCS: r = - 0.46, P = 0.003; MCS: r = - 0.37, P = 0.018), and SF-36 pain scores (r = - 0.63, P < 0.0001). Female sex was a risk factor for NP-like symptoms. Conclusions Pain was prevalent in controlled acromegaly patients, whereas NP-like symptoms were relatively infrequent, and only observed in females. NP-like symptoms were associated with lower HR-QoL in acromegaly. Since specific analgesic therapy is available, awareness for characterization, increased understanding, and clinical trials regarding neuropathic pain identification and treatment in acromegaly patients are warranted. Show less
Samson, S.L.; Nachtigall, L.B.; Fleseriu, M.; Gordon, M.B.; Bolanowski, M.; Labadzhyan, A.; ... ; Melmed, S. 2020
Purpose: The phase 3 CHIASMA OPTIMAL trial (NCT03252353) evaluated efficacy and safety of oral octreotide capsules (OOCs) in patients with acromegaly who previously demonstrated biochemical control... Show morePurpose: The phase 3 CHIASMA OPTIMAL trial (NCT03252353) evaluated efficacy and safety of oral octreotide capsules (OOCs) in patients with acromegaly who previously demonstrated biochemical control while receiving injectable somatostatin receptor ligands (SRLs).Methods: In this double-blind study, patients (N = 56) stratified by prior SRL dose were randomly assigned 1:1 to OOC or placebo for 36 weeks. The primary end point was maintenance of biochemical control at the end of treatment (mean insulin-like growth factor 1 [IGF-1] <= 1.0 x upper limit of normal [ULN]; weeks 34 and 36). Time to loss of IGF-1 response and proportion requiring reversion to injectable SRLs were assessed as broader control measures.Results: Mean IGF-1 measurements were 0.80 and 0.97 x ULN for OOC and 0.84 and 1.69 x ULN for placebo, at baseline and end of treatment, respectively. Mean growth hormone (GH) changed from 0.66 to 0.60 ng/mL for OOCs and 0.90 to 2.57 ng/mL for placebo. Normalization of IGF-1 levels (<= 1.0 x ULN) was maintained in 58.2% for OOCs vs 19.4% for placebo (P = .008); GH levels were maintained (< 2.5 ng/mL) in 77.7% for OOC vs 30.4% for placebo (P = .0007). Median time to loss of response (IGF-1 > 1.0 or >= 1.3 x ULN definitions) for patients receiving placebo was 16 weeks; for patients receiving OOCs, it was not reached for both definitions during the 36-week trial (P < .0001). Of the patients in the OOC group, 75% completed the trial on oral therapy. The OOC safety profile was consistent with previous SRL experience.Conclusions: OOCs may be an effective therapy for patients with acromegaly who previously were treated with injectable SRLs. Show less
Groot, S. de; Gelderblom, H.; Fiocco, M.; Bovee, J.V.M.G.; Hoeven, J.J.M. van der; Pijl, H.; Kroep, J.R. 2017
In this thesis, a number of observations are described in acromegaly patients with cured or biochemically well-controlled disease during long-term follow-up. These observations focus on the long... Show moreIn this thesis, a number of observations are described in acromegaly patients with cured or biochemically well-controlled disease during long-term follow-up. These observations focus on the long-term consequences of the disease on joints and bone. In addition, we investigated the role of the Growth Hormone (GH)/Insulin-like Growth Factor-1 (IGF-1) axis, including the possible effects of the exon 3 deleted GH receptor (d3-GHR) polymorphism, in patients with primary osteoarthritis (OA) that have serum IGF-1 levels within the normal range. Finally, we studied the long-term consequences of recombinant human GH (rhGH) replacement in GH Deficient (GHD) adults, focusing on the cardiovascular effects and the effects on bone in comparison to healthy controls. Show less
