Leflunomide exposure through second trimester of pregnancy: A case report.

Leflunomide is a commonly used disease modifying antirheumatic agent. However, its use is contraindicated in pregnancy. The American College of Rheumatology (ACR) guidelines recommend discontinuing Leflunomide at least 24 months before conception. If a woman is found to be pregnant while on Leflunomide, ACR suggests close monitoring and cholestyramine washout. We describe a case of a patient with a history of juvenile idiopathic arthritis who was on Leflunomide throughout the first and second trimester of her pregnancy. A cholestyramine washout regimen was started but not completed. The patient was induced at 37 weeks of gestation due to non-reassuring fetal heart rate. She ultimately delivered a healthy baby via emergency cesarian section.

Time perspective optimization promotes reflection and collaboration.

The present study demonstrated that an educational course designed to optimize the time perspective profile led to a significant increase in the adaptive judicial and external thinking style scores for the secondary school students in the experimental group compared with those in the control group.

Survey of medical oncologists and trainee practice on venous thromboembolism prophylaxis and treatment in solid cancers.

Venous thromboembolism (VTE) has a significant adverse impact on the outcomes of patients with active solid malignancies. Prophylaxis is indicated for cancer-associated VTE (CA-VTE) using the Khorana score for risk stratification. We surveyed medical oncology fellows and trainees regarding their practice in CA-VTE. Regarding treatment of CA-VTE, practice was consistent with guidelines. However, regarding prophylaxis for CA-VTE, there was a high degree of uncertainty, which highlights the need for ongoing education.

The mediating role of thinking styles in the relationship between adolescent time perspective and subjective well-being.

INTRODUCTION: The mechanism behind how time perspective (TP) relates to subjective well-being is not fully understood and thinking styles might be potential mediators. However, our understanding of the relationship between thinking styles and subjective well-being is currently limited to adult studies. This study aims to extend the literature by examining the mediating role of thinking styles in the relationship between TP and subjective well-being in an adolescent sample. METHODS: One hundred forty-nine male and one hundred and fourteen female secondary school students (13-18 years old) in Hong Kong responded to the Thinking Styles Inventory-Revised II (TSI-R2), the Zimbardo Time Perspective Inventory (ZTPI), the Positive and Negative Affect Schedule (PANAS), and the Temporal Satisfaction with Life Scale (TSWLS) in two waves separated by 2 months in 2017. RESULTS: After controlling for gender and TP, internal and external styles positively predicted positive affect and future life satisfaction after 2 months. Adaptive Type I hierarchical style positively predicted both positive and negative affect after 2 months, which supports the two-dimensional structure of affect. Unexpectedly, maladaptive Type II styles did not predict subjective well-being. Longitudinal mediation using cross-lagged panel model showed that thinking styles mediated three relationships between TP and subjective well-being. The internal style mediated the relationship between Past-Negative TP, positive affect, and future life satisfaction, while the external style mediated the relationship between Future TP and future life satisfaction. CONCLUSIONS: Thinking styles predicted adolescent subjective well-being and acted as mediators in the relationship between TPs and subjective well-being.

Tinzaparin for venous thromboembolism in patients with renal impairment: a single-centre, prospective pilot study.

BACKGROUND: Low molecular weight heparins (LMWH) are used extensively for prophylaxis and treatment of venous thromboembolism (VTE), bridging therapy for warfarin and standard of care in cancer-associated VTE (CA-VTE). Tinzaparin has the highest molecular weight of all LMWH and relies least on renal clearance to Cockcroft-Gault creatinine clearance (CrCl) of 20 mL/min. Previous pharmacological studies have demonstrated safety and effectiveness in elderly patients. Prospective clinical trials have confirmed these findings to CrCl 20 mL/min and in CA-VTE. We describe the pilot program developed at Concord Repatriation General Hospital for tinzaparin. AIMS: We aim to confirm the deliverability of tinzaparin in patients with renal insufficiency. METHODS: Twenty patients were established on tinzaparin as therapeutic anticoagulation with CrCl or CKD-EPI estimated glomerular filtration rate (eGFR) 20-50 mL/min with an indication for anticoagulation. Tinzaparin was given as a subcutaneous injection at 175 units/kg as a single daily dose, rounded to the nearest vial size. Tinzaparin anti-Xa levels were tested at Days 2, 7 and 14 (±1 day) and transition to oral anticoagulants were allowed at clinician discretion. RESULTS: No accumulation of tinzaparin was seen into Day 14. Two patients required dose-adjustment, five patients had bleeding complications (two major, three minor) and four patients died during follow-up, all attributable to patients' comorbidities. CrCl and body surface area-standardised CrCl were significantly correlated with tinzaparin anti-Xa level only on Day 2, and this effect was lost when patients with CrCl >50 mL/min were excluded. Data from our cohort confirm the deliverability of therapeutic tinzaparin in patients with CrCl or CKD-EPI eGFR 20-50 mL/min. Bleeding and death outcomes were also comparable to other trials using tinzaparin in CA-VTE. CONCLUSION: For patients with renal insufficiency, tinzaparin represents an attractive alternative anticoagulant with once-daily administration in a range of potential indications.

Measurement of procoagulant platelets provides mechanistic insight and diagnostic potential in heparin-induced thrombocytopenia.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a prothrombotic, immune-mediated adverse drug reaction associated with high rates of thrombosis-related morbidity and mortality caused by FcγRIIa-activating pathogenic antibodies to PF4-heparin. Procoagulant platelets are a platelet subset that promote thrombin generation, are clinically relevant in prothrombotic diseases, and are formed when platelet G-protein-coupled receptor (GPCR) and ITAM-linked receptors are co-stimulated. OBJECTIVES: We examined the procoagulant platelet response of healthy donors to platelet agonists in the presence of HIT plasma and determined the contribution of FcγRIIa. PATIENTS/METHODS: Our previously established flow cytometry-based procoagulant platelet assay was modified to incorporate plasma samples, performed using FcγRIIa-responsive donor platelets. Plasma samples were serotonin-release assay-confirmed HIT (HIT+), or negative on HIT screening. RESULTS: In response to GPCR stimulation, only HIT+ plasma produced a heparin-dependent sensitization that required active FcγRIIa. As a potential diagnostic tool, the procoagulant platelet assay achieved 98% accuracy in identifying clinically verified HIT when performed blinded to the diagnoses of a validation cohort. Samples inducing a higher procoagulant platelet response were more likely from patients with thrombotic complications. Thrombin stimulation markedly increased the procoagulant platelet response with HIT+ plasma that was heparin independent and only partially reversed by FcγRIIa blockade, possibly reflecting ongoing thrombotic risk after heparin cessation. CONCLUSIONS: We demonstrate that HIT plasma together with platelet agonists increased the procoagulant platelet proportions, which may contribute to thrombotic risk in HIT. Targeting procoagulant platelet activation may represent a novel treatment strategy. This assay may be a rapid, clinically relevant functional assay for accurately detecting pathological HIT antibodies.

Spontaneous Pneumomediastinum due to Anti-Melanoma Differentiation-Associated Protein 5 Requiring a Bilateral Lung Transplant.

Anti-melanoma differentiation-associated protein 5 (anti-MDA5) is a subset of dermatomyositis associated with respiratory complications, in which rapidly progressive interstitial lung disease (RPILD) is commonly cited, and spontaneous pneumomediastinum (SPM) is a rare complication. In medical literature, aggressive immunosuppressive therapy has been the mainstay of anti-MDA5-associated SPM management. Here, we report the first MDA5 case with SPM which was successfully treated with a double-lung transplant. We present a 48-year-old male who presented with multiple constitutional symptoms such as fevers, weight loss, malaise, and arthralgias, in association with erythroderma over the ears and fingers. Imaging of the chest demonstrated peripheral airspace disease, and myositis-specific serology returned positive for anti-Jo1 (medium-positive), anti-Ro52 (high-positive), and anti-MDA5 (weak-positive) autoantibodies. Therefore, the patient was begun on immunosuppressive therapy as the leading diagnosis included autoimmune myositis, possibly antisynthetase syndrome with interstitial lung disease (ILD). A year later, the patient presented with progressive shortness of breath, widespread macular erythematous facial rash, and new erythematous ulcerations over the fingertips. Imaging demonstrated a new SPM at this juncture. As the patient's respiratory status continued to decline despite the use of immunosuppressive agents, a double-lung transplant was performed. Therefore, we propose that lung transplantation should be considered early in MDA5-SPM.

Pralatrexate in relapsed/refractory T-cell lymphoma: a retrospective multicenter study.

We present a retrospective multicenter study of pralatrexate treatment outcomes in an Australian practice setting for patients with relapsed/refractory T-cell lymphoma who had failed 1+ systemic therapies, treated via a compassionate access program. Endpoints assessed included response rates, toxicities, and subsequent therapies. Progression-free survival (PFS), time to next treatment (TTNT), event-free survival (EFS), overall survival (OS), and time to best response, were assessed by Kaplan-Meier analysis. The study included 31 patients, with median age 69 years. We demonstrated ORR of 35.5% (n = 11), including 4 complete responses (13%) and 7 partial responses (23%). The predicted median OS was 10 months, with EFS of 9 months, and PFS of 9 months. Median TTNT was 8 months. Mucositis was the most commonly observed toxicity. This study - the second largest real-world cohort reported to date - underscores the importance of pralatrexate in relapsed/refractory T-cell lymphoma, as well as its acceptable toxicity profile.

T follicular helper phenotype predicts response to histone deacetylase inhibitors in relapsed/refractory peripheral T-cell lymphoma.

Histone deacetylase inhibitors (HDACi) are active agents for peripheral T-cell lymphoma (PTCL). Anecdotally angioimmunoblastic T-cell lymphoma (AITL) appears to respond better than PTCL-not otherwise specified (NOS) to HDACi. The new World Health Organization classification shows that a subgroup of PTCL carries similarities in phenotype and gene expression profiling to AITL, comparable to T follicular helper (TFH) cells. The disease might behave similarly to AITL when treated with HDACi. We analyzed 127 patients with AITL or PTCL-NOS treated with HDACi at relapse as a single agent or in combination. We re-reviewed the pathology of all PTCL-NOS to identify the TFH phenotype. Patients received HDACi at relapse as a single agent in 97 cases (76%, 59 TFH, 38 non-TFH) or in combination in 30 cases (24%, 18 TFH, 12 non-TFH) including duvelisib, lenalidomide, lenalidomide plus carfilzomib, and pralatrexate. Seven PTCL-NOS had TFH phenotype; 2 PTCL-NOS were reclassified as AITL. Overall response rate (ORR) was 56.5% (28.9% complete response [CR]) in TFH and 29.4% (19.6% CR) in non-TFH phenotype patients (P = .0035), with TFH phenotype being an independent predictor of ORR (P = .009). Sixteen patients sufficiently responded to HDACi or HDACi in combination with another agent to proceed directly to allogeneic transplantation; 1 of 16 responded to donor lymphocyte infusion (12 TFH, 4 non-TFH). Our results, although retrospective, support that HDACi, as a single agent or in combination, may have superior activity in TFH-PTCL compared with non-TFH PTCL. This differential efficacy could help inform subtype-specific therapy and guide interpretation of HDACi trials.

Clinical spectrum and therapeutics in Canadian patients with anti-melanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis: a case-based review.

The objective of the study was to determine the clinical features and treatment course in Canadian patients with dermatomyositis (DM) associated with the anti-melanoma differentiation-associated gene 5 antibody (MDA5). A retrospective chart review of consecutive patients with anti-MDA5 antibody DM from two Canadian tertiary care centre between 2014 and 2018 was done. Twenty-one consecutive cases of anti-MDA5-positive DM were identified. Median age at diagnosis was 52 years, 71% Asians, predominantly Chinese, and 29% Caucasians. In this case series, all patients had either typical DM rash, or vasculopathy and ulceration unique to anti-MDA5-positive DM. 38% of the patients had rapid progressive (RP)-interstitial lung disease (RP-ILD), 33% had chronic ILD and 29% had asymptomatic ILD. Anti-Ro52 positivity was more prevalent in RP-ILD. Mortality was high in the RP-ILD group, with five deaths in eight patients. Lung transplant was life-saving intervention for three of the RP-ILD patients who survived. A review of the literature in treating RP-ILD associated with anti-MDA5 is presented. Although evidence is limited to small case series, cyclophosphamide (CYC) for refractory skin lesions, and CYC or mycophenolate mofetil plus a calcineurin inhibitor or rituximab (RTX) for RP-ILD appear efficacious. This is the largest North American case series of anti-MDA5-positive DM patients to date. There is a wide spectrum of clinical presentation of this entity. Survival is poor in those with RP-ILD; early aggressive immunosuppression and timely lung transplant were life-saving in our patients with RP-ILD.

Bisphosphonates for steroid-induced osteoporosis.

BACKGROUND: This is an update of a Cochrane Review first published in 1999. Corticosteroids are widely used in inflammatory conditions as an immunosuppressive agent. Bone loss is a serious side effect of this therapy. Several studies have examined the use of bisphosphonates in the prevention and treatment of glucocorticosteroid-induced osteoporosis (GIOP) and have reported varying magnitudes of effect. OBJECTIVES: To assess the benefits and harms of bisphosphonates for the prevention and treatment of GIOP in adults. SEARCH METHODS: We searched CENTRAL, MEDLINE and Embase up to April 2016 and International Pharmaceutical Abstracts (IPA) via OVID up to January 2012 for relevant articles and conference proceedings with no language restrictions. We searched two clinical trial registries for ongoing and recently completed studies (ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal). We also reviewed reference lists of relevant review articles. SELECTION CRITERIA: We included randomised controlled trials (RCTs) satisfying the following criteria: 1) prevention or treatment of GIOP; 2) adults taking a mean steroid dose of 5.0 mg/day or more; 3) active treatment including bisphosphonates of any type alone or in combination with calcium or vitamin D; 4) comparator treatment including a control of calcium or vitamin D, or both, alone or with placebo; and 4) reporting relevant outcomes. We excluded trials that included people with transplant-associated steroid use. DATA COLLECTION AND ANALYSIS: At least two review authors independently selected trials for inclusion, extracted data, performed 'risk of bias' assessment and evaluated the certainty of evidence using the GRADE approach. Major outcomes of interest were the incidence of vertebral and nonvertebral fractures after 12 to 24 months; the change in bone mineral density (BMD) at the lumbar spine and femoral neck after 12 months; serious adverse events; withdrawals due to adverse events; and quality of life. We used standard Cochrane methodological procedures. MAIN RESULTS: We included a total of 27 RCTs with 3075 participants in the review. Pooled analysis for incident vertebral fractures included 12 trials (1343 participants) with high-certainty evidence and low risk of bias. In this analysis 46/597 (or 77 per 1000) people experienced new vertebral fractures in the control group compared with 31/746 (or 44 per 1000; range 27 to 70) in the bisphosphonate group; relative improvement of 43% (9% to 65% better) with bisphosphonates; absolute increased benefit of 2% fewer people sustaining fractures with bisphosphonates (5% fewer to 1% more); number needed to treat for an additional beneficial outcome (NNTB) was 31 (20 to 145) meaning that approximately 31 people would need to be treated with bisphosphonates to prevent new vertebral fractures in one person.Pooled analysis for incident nonvertebral fractures included nine trials with 1245 participants with low-certainty evidence (downgraded for imprecision and serious risk of bias as a patient-reported outcome). In this analysis 30/546 (or 55 per 1000) people experienced new nonvertebral fracture in the control group compared with 29/699 (or 42 per 1000; range 25 to 69) in the bisphosphonate group; relative improvement of 21% with bisphosphonates (33% worse to 53% better); absolute increased benefit of 1% fewer people with fractures with bisphosphonates (4% fewer to 1% more).Pooled analysis on BMD change at the lumbar spine after 12 months included 23 trials with 2042 patients. Eighteen trials with 1665 participants were included in the pooled analysis on BMD at the femoral neck after 12 months. Evidence for both outcomes was moderate-certainty (downgraded for indirectness as a surrogate marker for osteoporosis) with low risk of bias. Overall, the bisphosphonate groups reported stabilisation or increase in BMD, while the control groups showed decreased BMD over the study period. At the lumbar spine, there was an absolute increase in BMD of 3.5% with bisphosphonates (2.90% to 4.10% higher) with a relative improvement of 1.10% with bisphosphonates (0.91% to 1.29%); NNTB 3 (2 to 3). At the femoral neck, the absolute difference in BMD was 2.06% higher in the bisphosphonate group compared to the control group (1.45% to 2.68% higher) with a relative improvement of 1.29% (0.91% to 1.69%); NNTB 5 (4 to 7).Pooled analysis on serious adverse events included 15 trials (1703 participants) with low-certainty evidence (downgraded for imprecision and risk of bias). In this analysis 131/811 (or 162 per 1000) people experienced serious adverse events in the control group compared to 136/892 (or 147 per 1000; range 120 to 181) in the bisphosphonate group; absolute increased harm of 0% more serious adverse events (2% fewer to 2% more); a relative per cent change with 9% improvement (12% worse to 26% better).Pooled analysis for withdrawals due to adverse events included 15 trials (1790 patients) with low-certainty evidence (downgraded for imprecision and risk of bias). In this analysis 63/866 (or 73 per 1000) people withdrew in the control group compared to 76/924 (or 77 per 1000; range 56 to 107) in the bisphosphonate group; an absolute increased harm of 1% more withdrawals with bisphosphonates (95% CI 1% fewer to 3% more); a relative per cent change 6% worse (95% CI 47% worse to 23% better).Quality of life was not assessed in any of the trials. AUTHORS' CONCLUSIONS: There was high-certainty evidence that bisphosphonates are beneficial in reducing the risk of vertebral fractures with data extending to 24 months of use. There was low-certainty evidence that bisphosphonates may make little or no difference in preventing nonvertebral fractures. There was moderate-certainty evidence that bisphosphonates are beneficial in preventing and treating corticosteroid-induced bone loss at both the lumbar spine and femoral neck. Regarding harm, there was low-certainty evidence that bisphosphonates may make little or no difference in the occurrence of serious adverse events or withdrawals due to adverse events. We are cautious in interpreting these data as markers for harm and tolerability due to the potential for bias.Overall, our review supports the use of bisphosphonates to reduce the risk of vertebral fractures and the prevention and treatment of steroid-induced bone loss.

Neurite outgrowth in normal and injured primary sensory neurons reveals different regulation by nerve growth factor (NGF) and artemin.

Neurotrophic factors have been intensively studied as potential therapeutic agents for promoting neural regeneration and functional recovery after nerve injury. Artemin is a member of the glial cell line-derived neurotrophic factor (GDNF) family of ligands (GFLs) that forms a signalling complex with GFRα3 and the tyrosine kinase Ret. Systemic administration of artemin in rodents is reported to facilitate regeneration of primary sensory neurons following axotomy, improve recovery of sensory function, and reduce sensory hypersensitivity that is a cause of pain. However, the biological mechanisms that underlie these effects are mostly unknown. This study has investigated the biological significance of the colocalisation of GFRα3 with TrkA (neurotrophin receptor for nerve growth factor [NGF]) in the peptidergic type of unmyelinated (C-fibre) sensory neurons in rat dorsal root ganglia (DRG). In vitro neurite outgrowth assays were used to study the effects of artemin and NGF by comparing DRG neurons that were previously uninjured, or were axotomised in vivo by transecting a visceral or somatic peripheral nerve. We found that artemin could facilitate neurite initiation but in comparison to NGF had low efficacy for facilitating neurite elongation and branching. This low efficacy was not increased when a preconditioning in vivo nerve injury was used to induce a pro-regenerative state. Neurite initiation was unaffected by artemin when PI3 kinase and Src family kinase signalling were blocked, but NGF had a reduced effect.

Fistula use after concurrent arteriovenous fistula formation and Tenckhoff catheter insertion.

A significant proportion of peritoneal dialysis (PD) patients will have abrupt technique failure requiring conversion to haemodialysis, often using temporary vascular catheters as bridging access. However, vascular catheter use has been associated with increased mortality and great effort has been made to reduce their use. Just under two decades ago, a trial of dual arteriovenous fistula (AVF) formation and Tenckhoff catheter insertion reported only 4% of those in whom back-up fistulae were formed ever used them. Patient demographic, surgical technique and fistula care over those decades have changed substantially, potentially making this practice feasible. Thirty-five selected patients at Concord Repatriation and General Hospital had AVF formed at the time of Tenckhoff insertion and were entered prospectively into a vascular access database. We retrospectively examined this database with a median follow up of 345 days (interquartile range 183-658). Thirty-one per cent of all patients used the preformed AVF, and a further 19% who were still on PD had clinically functioning AVF. The vast majority (62%) had abrupt PD technique failure. This is a marked difference to dated reports of AVF use after concurrent PD and AVF formation. It raises the possibility that the formation of back-up fistula may be another method to reduce the need for vascular catheter use.

Inadequate knowledge of immunization guidelines: a missed opportunity for preventing infection in immunocompromised IBD patients.

BACKGROUND: Immunosuppressive agents, used commonly to treat inflammatory bowel disease (IBD), are associated with an increased risk of infections, including those preventable by immunization. This study aimed to describe physician and patient values and knowledge regarding immunization and immunization histories. METHODS: In all, 167 IBD patients and 43 gastroenterologists completed mail-out questionnaires. Patients were asked 15 questions about their immunization histories and attitudes towards immunization. Gastroenterologists were asked nine questions about immunization for the immunocompromised host. RESULTS: The questionnaire return rate was 45.7% (43/94) for gastroenterologists and 25.2% (167/661) for patients. Only 14.3% (6/42) of gastroenterologists reported taking an immunization history from most or all of their patients. Only 5.4% (9/167) of patients recalled being asked by their gastroenterologist whether their immunizations were up to date, and just 0.6% (1/164) recalled being asked for a detailed immunization history. Overall, 21.7% (35/161) of patients had refused to be immunized in the past; 18.6% (8/43) of gastroenterologists did not know if up-to-date immunizations were important prior to starting immunosuppressive therapy. Of note, 23.1% (9/39) of gastroenterologists and 46.7% (35/161) of patients did not know whether live vaccines should be avoided by those in the immunosuppressed state, and 42.9% (18/43) of gastroenterologists acknowledged they did not know which specific immunizations should be avoided for immunosuppressed patients. CONCLUSIONS: Gastroenterologists have limited knowledge of their IBD patients' immunization status and rarely take an adequate immunization history. Substantial proportions of IBD patients and gastroenterologists lack adequate knowledge of established immunization guidelines prior to initiation of immunosuppressive therapy.

Antineoplastic effects of an Aurora B kinase inhibitor in breast cancer.

BACKGROUND: Aurora B kinase is an important mitotic kinase involved in chromosome segregation and cytokinesis. It is overexpressed in many cancers and thus may be an important molecular target for chemotherapy. AZD1152 is the prodrug for AZD1152-HQPA, which is a selective inhibitor of Aurora B kinase activity. Preclinical antineoplastic activity of AZD1152 against acute myelogenous leukemia, multiple myeloma and colorectal cancer has been reported. However, this compound has not been evaluated in breast cancer, the second leading cause of cancer deaths among women. RESULTS: The antineoplastic activity of AZD1152-HQPA in six human breast cancer cell lines, three of which overexpress HER2, is demonstrated. AZD1152-HQPA specifically inhibited Aurora B kinase activity in breast cancer cells, thereby causing mitotic catastrophe, polyploidy and apoptosis, which in turn led to apoptotic death. AZD1152 administration efficiently suppressed the tumor growth in a breast cancer cell xenograft model. In addition, AZD1152 also inhibited pulmonary metastatic nodule formation in a metastatic breast cancer model. Notably, it was also found that the protein level of Aurora B kinase declined after inhibition of Aurora B kinase activity by AZD1152-HQPA in a time- and dose-dependent manner. Investigation of the underlying mechanism suggested that AZD1152-HQPA accelerated protein turnover of Aurora B via enhancing its ubiquitination. CONCLUSIONS: It was shown that AZD1152 is an effective antineoplastic agent for breast cancer, and our results define a novel mechanism for posttranscriptional regulation of Aurora B after AZD1152 treatment and provide insight into dosing regimen design for this kinase inhibitor in metastatic breast cancer treatment.

Phonetic complexity and stuttering in Spanish.

The current study investigated whether phonetic complexity affected stuttering rate for Spanish speakers. The speakers were assigned to three age groups (6-11, 12-17 and 18-years plus) that were similar to those used in an earlier study on English. The analysis was performed using Jakielski's Index of Phonetic Complexity (IPC) scheme in which each word is given an IPC score based on the number of complex attributes it includes for each of eight factors. Stuttering on function words for Spanish did not correlate with IPC score for any age group. This mirrors the finding for English that stuttering on these words is not affected by phonetic complexity. The IPC scores of content words correlated positively with stuttering rate for 6-11-year-old and adult speakers. Comparison was made between the languages to establish whether or not experience with the factors determines the problem they pose for speakers (revealed by differences in stuttering rate). Evidence was obtained that four factors found to be important determinants of stuttering on content words in English for speakers aged 12 and above, also affected Spanish speakers. This occurred despite large differences in frequency of usage of these factors. It is concluded that phonetic factors affect stuttering rate irrespective of a speaker's experience with that factor.