Overview of global real-world data sources for pediatric pharmacoepidemiologic research.

PURPOSE: Given limited information available on real-world data (RWD) sources with pediatric populations, this study describes features of globally available RWD sources for pediatric pharmacoepidemiologic research. METHODS: An online questionnaire about pediatric RWD sources and their attributes and capabilities was completed by members and affiliates of the International Society for Pharmacoepidemiology and representatives of nominated databases. All responses were verified by database representatives and summarized. RESULTS: Of 93 RWD sources identified, 55 unique pediatric RWD sources were verified, including data from Europe (47%), United States (38%), multiregion (7%), Asia-Pacific (5%), and South America (2%). Most databases had nationwide coverage (82%), contained electronic health/medical records (47%) and/or administrative claims data (42%) and were linkable to other databases (65%). Most (71%) had limited outside access (e.g., by approval or through local collaborators); only 10 (18%) databases were publicly available. Six databases (11%) reported having >20 million pediatric observations. Most (91%) included children of all ages (birth until 18th birthday) and contained outpatient medication data (93%), while half (49%) contained inpatient medication data. Many databases captured vaccine information for children (71%), and one-third had regularly updated data on pediatric height (31%) and weight (33%). Other pediatric data attributes captured include diagnoses and comorbidities (89%), lab results (58%), vital signs (55%), devices (55%), imaging results (42%), narrative patient histories (35%), and genetic/biomarker data (22%). CONCLUSIONS: This study provides an overview with key details about diverse databases that allow researchers to identify fit-for-purpose RWD sources suitable for pediatric pharmacoepidemiologic research.

Association between glycemic control and risk of venous thromboembolism in diabetic patients: a nested case-control study.

BACKGROUND: Previous studies suggested an elevated risk of venous thromboembolism (VTE) among patients with type 2 diabetes mellitus (T2DM), with a possible sex difference. The impact of glycemic control on the risk of VTE is unclear. Our objective was to analyze the association between glycemic control and the risk of unprovoked (idiopathic) VTE in men and women with T2DM. METHODS: We conducted a nested case-control analysis (1:4 matching) within a cohort of patients with incident T2DM between 1995 and 2019 using data from the CPRD GOLD. We excluded patients with known risk factors for VTE prior to onset of DM. Cases were T2DM patients with an unprovoked treated VTE. The exposure of interest was glycemic control measured as HbA1c levels. We conducted conditional logistic regression analyses adjusted for several confounders. RESULTS: We identified 2'653 VTE cases and 10'612 controls (53.1% females). We found no association between the HbA1c level and the risk of VTE in our analyses. However, when the most recent HbA1c value was recorded within 90 days before the index date, women with HbA1c levels > 7.0% had a 36-55% increased relative risk of VTE when compared to women with HbA1c > 6.5-7.0%. CONCLUSIONS: Our study raises the possibility that female T2DM patients with HbA1c levels > 7% may have a slightly higher risk for unprovoked VTE compared to women with HbA1c levels > 6.5-7.0%. This increase may not be causal and may reflect differences in life style or other characteristics. We observed no effect of glycemic control on the risk of VTE in men.

Understanding the links between cardiovascular disease and Parkinson's disease.

Studies investigating the associations between genetic or environmental factors and Parkinson's disease (PD) have uncovered a number of factors shared with cardiovascular disease, either as risk factors or manifestations of cardiovascular disease itself. Older age, male sex, and possibly type 2 diabetes are examples. On the other hand, coffee consumption and physical activity are each associated with a lower risk of both PD and cardiovascular disease. This observation raises questions about the underlying pathophysiological links between cardiovascular disease and PD. There is evidence for common mechanisms in the areas of glucose metabolism, cellular stress, lipid metabolism, and inflammation. On the other hand, smoking and total/low-density lipoprotein cholesterol appear to have opposite associations with cardiovascular disease and PD. Thus, it is uncertain whether the treatment of cardiovascular risk factors will impact on the onset or progression of PD. The available data suggest that a nuanced approach is necessary to manage risk factors such as cholesterol levels once the associations are better understood. Ultimately, the choice of therapy may be tailored to a patient's comorbidity profile. This review presents the epidemiological evidence for both concordant and discordant associations between cardiovascular disease and PD, discusses the cellular and metabolic processes that may underlie these links, and explores the implications this has for patient care and future research. © 2019 International Parkinson and Movement Disorder Society.

Use of selective serotonin reuptake inhibitors, other antidepressant medication, and risk of cataract: a case-control study based on Swiss claims data.

PURPOSE: Three previous studies reported controversial results regarding selective serotonin reuptake inhibitor (SSRI) exposure and cataract development. We therefore aimed to assess risk of cataract associated with previous exposure to SSRI using data from a large health insurance in Switzerland. METHODS: In a case-control study, we analyzed individuals insured by the Helsana Group, a large Swiss health insurance provider. We matched patients aged 40 years or older with cataract extraction (i.e., a proxy for a cataract diagnosis) in 2014 or 2015 to four control patients, on age, sex, date of cataract extraction, and area of residence. Exposure of interest was the number of SSRI claims prior to cataract extraction. We conducted conditional logistic regression analyses to calculate odds ratios (OR) with 95% confidence intervals (CI). We adjusted our analyses for the presence of hypertension, diabetes, glaucoma, systemic steroid use, and use of other antidepressant drugs. RESULTS: We identified 13,773 cataract cases and 51,625 matched controls. Compared with non-use, long-term use of SSRI (≥ 20 claims) was not associated with an altered risk of cataract (adjusted OR 0.93, 95% CI 0.84-1.04). The analysis of the individual drug substances also yielded no statistically significant association between drug exposure and the risk of cataract. CONCLUSIONS: According to our study, use of SSRI does not change the risk of cataract in the overall population.

Parkinson disease and the risk of epileptic seizures.

OBJECTIVE: To assess the association between incident Parkinson disease (PD) and subsequent incident epileptic seizures. METHODS: We conducted a retrospective cohort study with a nested case-control analysis using data from the U.K. Clinical Practice Research Datalink. We identified patients aged ≥40 years with an incident diagnosis of PD between 1995 and 2016 and a matched comparison group of PD-free individuals. We calculated crude incidence rates (IRs) with 95% confidence intervals (CIs) of epileptic seizures in PD patients and the PD-free comparison group, and corresponding crude incidence rate ratios (IRRs). In the nested case-control analysis, we calculated adjusted odds ratios (adj. ORs) of incident PD among cases with incident epileptic seizures and seizure-free controls overall and stratified by various seizure-provoking comorbidities. RESULTS: Among 23,086 incident PD patients and 92,343 PD-free individuals, we identified 898 patients with incident epileptic seizures. The crude IR of epileptic seizures in PD patients was 266.7/100,000 person-years (95% CI = 235.6-297.7), and in PD-free individuals it was 112.4/100,000 person-years (95% CI = 103.5-121.3; IRR = 2.37, 95% CI = 2.06-2.73). The adj. OR of epileptic seizures was 1.68 (95% CI = 1.43-1.98) in PD patients compared with PD-free individuals. PD patients with comorbid brain disorders (adj. OR = 12.36, 95% CI = 8.74-17.48) or with > 1 seizure-provoking comorbidity (adj. OR = 13.24, 95% CI = 10.15-17.25) were at the highest risk of epileptic seizures compared with PD-free individuals with no seizure-provoking comorbidities. INTERPRETATION: This study suggests that incident PD is associated with an increased risk of incident epileptic seizures. Ann Neurol 2018;83:363-374.

Selective Serotonin Reuptake Inhibitors and Cataract Risk: A Case-Control Analysis.

PURPOSE: Use of selective serotonin reuptake inhibitors (SSRIs) has been associated with an increased cataract risk. We aimed to assess cataract risk after exposure to SSRI or to other antidepressant drugs in a large electronic primary care database. DESIGN: Case-control study. PARTICIPANTS: The study population was derived from the UK-based Clinical Practice Research Datalink (CPRD). We included patients with first-time cataract aged ≥40 years between 1995 and 2015 and an equal number of cataract-free controls matched on age, sex, general practice, date of cataract recording (i.e., index date), and years of history in the CPRD before the index date. METHODS: We conducted conditional logistic regression analyses adjusted for body mass index, smoking, hypertension, diabetes, and systemic steroid use. Exposure of interest was the number of SSRI prescriptions and prescriptions for other antidepressant drugs. We further explored mutually exclusive use of single SSRI substances. In sensitivity analyses, we shifted the index date backwards by 2 years, and we restricted our analyses to cases and controls without a prior glaucoma diagnosis. MAIN OUTCOME MEASURES: Relative risk estimates as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: We identified 206 931 cataract cases and the same number of matched controls. Current long-term use of SSRI (≥20 prescriptions) was not associated with an increased cataract risk (adjusted OR, 0.99; 95% CI, 0.94-1.03). However, in a subset of patients aged 40 to 64 years, we found a slightly increased risk of cataract for long-term SSRI users (adjusted OR, 1.24; 95% CI, 1.15-1.34) compared with nonusers. CONCLUSIONS: In these data, use of SSRI was not associated with an increased risk of cataract. The slightly increased OR for individuals younger than 65 years of age in association with long-term SSRI use needs to be investigated in further studies.

Comparative Effects of Volutrauma and Atelectrauma on Lung Inflammation in Experimental Acute Respiratory Distress Syndrome.

OBJECTIVE: Volutrauma and atelectrauma promote ventilator-induced lung injury, but their relative contribution to inflammation in ventilator-induced lung injury is not well established. The aim of this study was to determine the impact of volutrauma and atelectrauma on the distribution of lung inflammation in experimental acute respiratory distress syndrome. DESIGN: Laboratory investigation. SETTING: University-hospital research facility. SUBJECTS: Ten pigs (five per group; 34.7-49.9 kg) INTERVENTIONS: : Animals were anesthetized and intubated, and saline lung lavage was performed. Lungs were separated with a double-lumen tube. Following lung recruitment and decremental positive end-expiratory pressure trial, animals were randomly assigned to 4 hours of ventilation of the left (ventilator-induced lung injury) lung with tidal volume of approximately 3 mL/kg and 1) high positive end-expiratory pressure set above the level where dynamic compliance increased more than 5% during positive end-expiratory pressure trial (volutrauma); or 2) low positive end-expiratory pressure to achieve driving pressure comparable with volutrauma (atelectrauma). The right (control) lung was kept on continuous positive airway pressure of 20 cm H2O, and CO2 was partially removed extracorporeally. MEASUREMENTS AND MAIN RESULTS: Regional lung aeration, specific [F]fluorodeoxyglucose uptake rate, and perfusion were assessed using computed and positron emission tomography. Volutrauma yielded higher [F]fluorodeoxyglucose uptake rate in the ventilated lung compared with atelectrauma (median [interquartile range], 0.017 [0.014-0.025] vs 0.013 min [0.010-0.014 min]; p < 0.01), mainly in central lung regions. Volutrauma yielded higher [F]fluorodeoxyglucose uptake rate in ventilator-induced lung injury versus control lung (0.017 [0.014-0.025] vs 0.011 min [0.010-0.016 min]; p < 0.05), whereas atelectrauma did not. Volutrauma decreased blood fraction at similar perfusion and increased normally as well as hyperaerated lung compartments and tidal hyperaeration. Atelectrauma yielded higher poorly and nonaerated lung compartments, and tidal recruitment. Driving pressure increased in atelectrauma. CONCLUSIONS: In this model of acute respiratory distress syndrome, volutrauma promoted higher lung inflammation than atelectrauma at comparable low tidal volume and lower driving pressure, suggesting that static stress and strain are major determinants of ventilator-induced lung injury.

Statin use and risk of glioma: population-based case-control analysis.

Statins have been reported to decrease the incidence of cancer, but the risk of glioma among statin users has been investigated in only two prior observational studies, both of them suggesting a modest protective effect of statins. We conducted a matched case-control study using data from the UK-based Clinical Practice Research Datalink to analyse use of statins among 2469 cases with glioma and 24,690 controls. We performed conditional logistic regression analysis to calculate relative risks, estimated as odds ratios (ORs) with 95 % confidence intervals (CIs) adjusting for multiple confounding factors. As compared with non-use of statins, use of statins was not associated with risk of glioma (OR for ≥90 prescriptions=0.75; 95 % CI 0.48-1.17). Our findings do not support previous sparse evidence of a possible inverse association between statin use and glioma risk.

Evaluating different physician's prescribing preference based instrumental variables in two primary care databases: a study of inhaled long-acting beta2-agonist use and the risk of myocardial infarction.

PURPOSE: Instrumental variable (IV) analysis with physician's prescribing preference (PPP) as IV is increasingly used in pharmacoepidemiology. However, it is unclear whether this IV performs consistently across databases. We aimed to evaluate the validity of different PPPs in a study of inhaled long-acting beta2-agonist (LABA) use and myocardial infarction (MI). METHODS: Information on adults with asthma and/or COPD and at least one prescription of beta2-agonist, or muscarinic antagonist was extracted from the CPRD (UK) and the Mondriaan (Netherlands) databases. LABA exposure was considered time-fixed or time-varying. We measured PPPs using previous LABA prescriptions of physicians or proportion of LABA prescriptions per practice. Correlation (r) and standardized difference (SDif) were used to assess assumption of IV analysis. RESULTS: For time-fixed LABA, the IV based on 10 previous prescriptions outperformed the other IVs regarding strength of the IV (r ≥ 0.15) and balance of confounders between IV categories (SDif < 0.10). None of the IVs we considered appeared to be valid for time-varying LABA. In CPRD (n = 490,499), which included approximately 18 times more subjects than Mondriaan (n = 27,459), IVs appeared more valid. LABA was not associated with MI; hazard ratios ranged from 0.86 to 1.18 for conventional analysis, and from 0.61 to 1.24 for the IV analyses with apparent valid IVs. CONCLUSIONS: The validity of physician's prescribing preference as IV strongly depends on how this IV is defined and in which database it is applied. Hence, general recommendations cannot be made, other than to generate several plausible IVs, assess their validity, and report the estimate(s) from apparently valid IVs.

Non-steroidal anti-inflammatory drugs and the risk of head and neck cancer: A case-control analysis.

Non-steroidal anti-inflammatory drugs (NSAIDs) and acetylsalicylic acid (aspirin) have been associated with a reduced risk for certain cancers. We explored the association between use of NSAIDs and the risk of head and neck cancer (HNC). We conducted a case-control analysis in the UK-based Clinical Practice Research Datalink (CPRD) among people below the age of 90 years with incident HNC between 1995 and 2013. Six controls per case were matched on age, sex, calendar time, general practice, and number of years of active history in the CPRD prior to the HNC diagnosis. Other potential confounders including comorbidities and comedication were also evaluated, and we adjusted our final analyses for BMI, smoking and alcohol consumption. Our analyses included 2,745 HNC cases and 16,470 controls. Aspirin or NSAID use overall did not significantly change the HNC risk. However, patients with six or more prescriptions for ibuprofen were at a statistically significantly reduced risk for HNC (adjusted OR 0.59, 95% CI 0.37-0.94). The HNC risk tended to decrease with increasing cumulative exposure to ibuprofen, and to be more pronounced for cancer of the larynx. To conclude, in this large population-based observational study we found a decreased risk for HNC associated with regular use of ibuprofen.

No evidence for a decreased risk of thyroid cancer in association with use of metformin or other antidiabetic drugs: a case-control study.

BACKGROUND: Use of metformin has been associated with a decreased cancer risk. We aimed to explore whether use of metformin or other antidiabetic drugs is associated with a decreased risk for thyroid cancer. METHODS: We conducted a case-control analysis (1995 to 2014) using the U.K.-based Clinical Practice Research Datalink (CPRD). Cases had a first-time diagnosis of thyroid cancer, six controls per case were matched on age, sex, calendar time, general practice, and number of years of active history in the database prior to the index date. We assessed odds ratios (ORs) with 95 % confidence intervals (95 % CI), adjusted for body mass index (BMI), smoking, and diabetes mellitus. RESULTS: In 1229 cases and 7374 matched controls, the risk of thyroid cancer associated with ever use of metformin yielded an adjusted OR of 1.48, 95 % CI 0.86-2.54. The relative risk estimate was highest in long-term (≥30 prescriptions) users of metformin (adjusted OR 1.83, 95 % CI 0.92-3.65), based on a limited number of 26 exposed cases. No such association was found in users of sulfonylurea, insulin, or thiazolidinediones (TZD). Neither a diabetes diagnosis (adjusted OR 1.17, 95 % CI 0.89-1.54), nor diabetes duration >8 years (adjusted OR 1.22, 95 % CI 0.60-2.51) altered the risk of thyroid cancer. CONCLUSION: In our observational study with limited statistical power, neither use of metformin nor of other antidiabetic drugs were associated with a decreased risk of thyroid cancer.

Case-control analysis on metformin and cancer of the esophagus.

PURPOSE: Metformin use has been associated with decreased cancer risks, though data on esophageal cancer are scarce. We explored the relation between use of metformin or other anti-diabetic drugs and the risk of esophageal cancer. METHODS: We conducted a case-control analysis in the UK-based general practice research database (GPRD, now clinical practice research datalink, CPRD). Cases were individuals with an incident diagnosis of esophageal cancer between 1994 and 2010 at age 40-89 years. Ten controls per case were matched on age, sex, calendar time, general practice, and number of years of active history in the GPRD prior to the index date. Various potential confounders including diabetes mellitus, gastro-esophageal reflux, and use of proton-pump inhibitors were evaluated in univariate models, and the final results were adjusted for BMI and smoking. Results are presented as odds ratios (ORs) with 95 % confidence intervals (CI). RESULTS: Long-term use (≥30 prescriptions) of metformin was not associated with a materially altered risk of esophageal cancer (adj. OR 1.23, 95 % CI 0.92-1.65), nor was long-term use of sulfonylureas (adj. OR 0.93, 95 % CI 0.70-1.23), insulin (adj. OR 0.87, 95 % CI 0.60-1.25), or of thiazolidinediones (adj. OR 0.71, 95 % CI 0.37-1.36). CONCLUSION: In our population-based study, use of metformin was not associated with an altered risk of esophageal cancer.

Metformin and the risk of endometrial cancer: a case-control analysis.

OBJECTIVE: To explore the risk of endometrial cancer in relation to metformin and other antidiabetic drugs. METHODS: We conducted a case-control analysis to explore the association between use of metformin and other antidiabetic drugs and the risk of endometrial cancer using the UK-based General Practice Research Database (GPRD). Cases were women with an incident diagnosis of endometrial cancer, and up to 6 controls per case were matched in age, sex, calendar time, general practice, and number of years of active history in the GPRD prior to the index date. Odds ratios (ORs) with 95% confidence intervals (95% CI) were calculated and results were adjusted by multivariate logistic regression analyses for BMI, smoking, a recorded diagnosis of diabetes mellitus, and diabetes duration. RESULTS: A total of 2554 cases with incident endometrial cancer and 15,324 matched controls were identified. Ever use of metformin compared to never use of metformin was not associated with an altered risk of endometrial cancer (adj. OR 0.86, 95% CI 0.63-1.18). Stratified by exposure duration, neither long-term (≥25 prescriptions) use of metformin (adj. OR 0.79, 95% CI 0.54-1.17), nor long-term use of sulfonylureas (adj. OR 0.96, 95% CI 0.65-1.44), thiazolidinediones (≥15 prescriptions; adj. OR 1.22, 95% CI 0.67-2.21), or insulin (adj. OR 1.05 (0.79-1.82) was associated with the risk of endometrial cancer. CONCLUSION: Use of metformin and other antidiabetic drugs were not associated with an altered risk of endometrial cancer.

Contemporary Approaches Toward Neuromodulation of Fear Extinction and Its Underlying Neural Circuits.

Neuroscience and neuroimaging research have now identified brain nodes that are involved in the acquisition, storage, and expression of conditioned fear and its extinction. These brain regions include the ventromedial prefrontal cortex (vmPFC), dorsal anterior cingulate cortex (dACC), amygdala, insular cortex, and hippocampus. Psychiatric neuroimaging research shows that functional dysregulation of these brain regions might contribute to the etiology and symptomatology of various psychopathologies, including anxiety disorders and post traumatic stress disorder (PTSD) (Barad et al. Biol Psychiatry 60:322-328, 2006; Greco and Liberzon Neuropsychopharmacology 41:320-334, 2015; Milad et al. Biol Psychiatry 62:1191-1194, 2007a, Biol Psychiatry 62:446-454, b; Maren and Quirk Nat Rev Neurosci 5:844-852, 2004; Milad and Quirk Annu Rev Psychol 63:129, 2012; Phelps et al. Neuron 43:897-905, 2004; Shin and Liberzon Neuropsychopharmacology 35:169-191, 2009). Combined, these findings indicate that targeting the activation of these nodes and modulating their functional interactions might offer an opportunity to further our understanding of how fear and threat responses are formed and regulated in the human brain, which could lead to enhancing the efficacy of current treatments or creating novel treatments for PTSD and other psychiatric disorders (Marin et al. Depress Anxiety 31:269-278, 2014; Milad et al. Behav Res Ther 62:17-23, 2014). Device-based neuromodulation techniques provide a promising means for directly changing or regulating activity in the fear extinction network by targeting functionally connected brain regions via stimulation patterns (Raij et al. Biol Psychiatry 84:129-137, 2018; Markovic et al. Front Hum Neurosci 15:138, 2021). In the past ten years, notable advancements in the precision, safety, comfort, accessibility, and control of administration have been made to the established device-based neuromodulation techniques to improve their efficacy. In this chapter we discuss ten years of progress surrounding device-based neuromodulation techniques-Electroconvulsive Therapy (ECT), Transcranial Magnetic Stimulation (TMS), Magnetic Seizure Therapy (MST), Transcranial Focused Ultrasound (TUS), Deep Brain Stimulation (DBS), Vagus Nerve Stimulation (VNS), and Transcranial Electrical Stimulation (tES)-as research and clinical tools for enhancing fear extinction and treating PTSD symptoms. Additionally, we consider the emerging research, current limitations, and possible future directions for these techniques.

Antimicrobial drug use and the risk of glioma: A case-control study.

BACKGROUND: The use of antibiotics has been associated with increased risks of various cancers. Comprehensive information on the association of antibiotic use with the risk of glioma is lacking. METHODS: We performed a large case-control study based on the Clinical Practice Research Datalink (CPRD) GOLD from the United Kingdom. We identified 4423 glioma cases recorded between 1995 and 2020 and matched them to controls (1:10) on the date of diagnosis (i.e., the index date), age, sex, general practice, and number of years of medical history in the database prior to the index date. We conducted conditional logistic regression analyses to calculate odds ratios (ORs) with 95% confidence intervals (CIs). The exposures of interest were the use of antimicrobial drugs, including antibacterial, antiviral, antifungal, antiprotozoal, and anthelmintic drugs with specific subclasses, where possible. RESULTS: We found no substantially increased risk of glioma after ever-use of antibiotics (OR 1.13, 95% CI 1.03-1.24). The risk did not increase with the increasing number of prescriptions received or with increasing time from first use to cancer diagnosis. The use of polyenes was associated with a weakly decreased risk of glioma (OR 0.81, 95% CI 0.67-0.96).

Use of antidiabetic agents and the risk of pancreatic cancer: a case-control analysis.

OBJECTIVES: The objective of this study was to explore the association between use of metformin or other antidiabetic drugs, diabetes, and the risk of pancreatic cancer. METHODS: We conducted a case-control study using the UK-based General Practice Research Database (GPRD). Cases had a first-time diagnosis of pancreatic cancer, and six controls per case were matched on age, sex, calendar time, general practice, and number of years of active history in the GPRD before the index date. Results were further adjusted in multivariate logistic regression analyses for potential confounders such as body mass index, smoking, alcohol consumption, and diabetes duration. RESULTS: In all, 2,763 case patients with a recorded diagnosis of pancreatic cancer were identified. Mean age ± s.d. was 69.5 ± 11.0 years. Long-term use (≥ 30 prescriptions) of metformin was not associated with a materially altered risk of pancreatic cancer (adjusted odds ratio (adj. OR): 0.87, 95% confidence interval (CI): 0.59-1.29), but there was a suggestion of effect modification by gender, as long-term use of metformin was linked to a decreased risk in women (adj. OR: 0.43, 95% CI: 0.23-0.80). Both use of sulfonylureas (≥ 30 prescriptions, adj. OR: 1.90, 95% CI: 1.32-2.74) and of insulin (≥ 40 prescriptions, adj. OR: 2.29, 95% CI: 1.34-3.92) were associated with an increased risk of pancreatic cancer. CONCLUSIONS: Use of metformin was associated with a decreased risk of pancreatic cancer in women only, whereas use of sulfonylureas and of insulin was associated with an increased risk of pancreatic cancer.

Population structure and forensic genetic analyses in Guarani and Kaingang Amerindian populations from Brazil.

When DNA profile comparisons between a crime scene trace and a reference sample generate correspondence, the match probability has to be estimated, so that evaluation of the strength of the forensic DNA evidence can be made. The random match probability estimations require information on allele frequencies and an adjustment factor, referred to as theta (θ) or Fst, a co-ancestry correction factor for subpopulation effects. The θ value has been standardized for urban and isolated populations, but inconsistencies have been reported when it is specifically calculated for smaller and isolated populations, including Amerindian populations. Notably, attempts to characterize forensic markers of these minor populations have been extensively limited and more conservative estimates of the correction factor may be generated for each of them. Therefore, we estimate allele frequencies of 21 autosomal STR markers used for forensic testing and calculated relevant forensic parameters for the set. In addition, we featured the possible structure of five Brazilian Amerindian populations that have been genetically isolated for centuries so we could obtain the appropriate θ value for them. The sample consisted of 319 individuals: (1) 121 Kaingang, from two communities: Ivaí (KIV=61) and Rio das Cobras (KRC=60); and (2) 198 Guaranis from three communities: Mbya from Rio das Cobras (GRC=51), Guarani Ñandeva (GND=71) and Guarani Kaiowá (GKW=76). Between Guarani populations low (Rst=0.0402, p < 10-4) to high (Rst=0.1557, p < 10-5) differentiation was found. Regarding Guarani and Kaingang populations, intermediate (Rst=0.0590, p < 10-5) to high (Rst=0.1604, p < 10-5) differentiation was found. The two Kaingang populations showed very low differentiation between them (Rst=0.0017, p = 0.27), which justifies the union of both genetic data for forensic databases and calculations. The combined power of discrimination (PD) and the combined power of exclusion (PE) were calculated for each population, demonstrating the usefulness of this set of markers in forensic and kinship analysis regarding these populations. Considering the demographic heterogeneity of Amerindian populations in general, the Fst mean value (0.03) was evaluated regarding 43 different indigenous populations from the Americas, including Guaranis and Kaingangs. This result confirms the adequacy of the standardized θ value for the forensic random match probability estimations involving Amerindian populations.