A Case of Burnt-Out Langerhans Cell Histiocytosis Presenting as Postpartum Hypopituitarism.

OBJECTIVE: To evaluate the case of a woman who presented with central hypogonadism and diabetes insipidus and further developed a persistent cough leading to an unexpected diagnosis of burnt-out Langerhans cell histiocytosis (LCH). METHODS: Clinical and laboratory endocrine evaluation, magnetic resonance imaging, high-resolution computed tomography, and open-lung biopsy results are discussed. RESULTS: A 28-year-old woman presented at 10 months postpartum with polydipsia, polyuria, and amenorrhea for 3 months. Her results showed a prolactin level of 25 µg/L (reference,<23.5 µg/L), estrogen level of 91 pmol/L (reference, 110-180 pmol/L), follicle-stimulating hormone level of 6 IU/L (reference, 2-20 IU/L), and luteinizing hormone level of 6 IU/L (reference, 2-70 IU/L). A water-deprivation test found a sodium concentration of 148 mmol/L (reference, 135-145 mmol/L), serum osmolality of 310 mmol/kg (reference, 275-295 mmol/kg), and urine osmolality of 107 mmol/kg (reference, 50-1450 mmol/kg) that improved to 142 mEq/L, 295 mmol/kg, and 535 mmol/kg, respectively, after desmopressin administration. Gadolinium-enhanced pituitary magnetic resonance imaging demonstrated a markedly thickened stalk with uniform enhancement. Chest high-resolution computed tomography confirmed bilateral upper-zone cystic lung disease suggestive of either pulmonary lymphangioleiomyomatosis or LCH. Eventual histology showed CD1a-positive burnt-out LCH. This differentiation was crucial as pulmonary lymphangioleiomyomatosis exacerbates with estrogen therapy and pregnancy, which the patient was able to successfully pursue without disease exacerbation. CONCLUSION: The patient's initial presentation was considered as lymphocytic hypophysitis, but subsequent cystic changes on high-resolution computed tomography led to a unifying definitive diagnosis of burnt-out LCH. This case highlights the importance of investigating for uncommon secondary causes of hypophysitis.

Salvage systemic therapy for advanced gastric and oesophago-gastric junction adenocarcinoma.

BACKGROUND: Salvage systemic therapy has become the new standard of care in patients with advanced gastric and oesophago-gastric junction (OGJ) adenocarcinoma, following disease progression on first-line fluoropyrimidine and platinum-containing chemotherapy. Pharmacological agents proven to be effective in this setting include both chemotherapy and biological therapy, however, the consensus on the best salvage systemic therapy has not been reached. OBJECTIVES: To assess the effects of systemic chemotherapy and biological therapy, either alone or in combination, on overall survival (OS) and progression-free survival (PFS) in patients with advanced gastric and OGJ adenocarcinoma, whose disease has progressed on, or relapsed after first-line fluoropyrimidine and platinum-containing chemotherapy. Adverse events (AEs), tumour response rate (TRR) and quality of life (QoL) associated with systemic chemotherapy and/or biological therapy were additionally assessed. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, trial registries and proceedings of the major oncology conferences up to October 2020. We additionally handsearched the reference lists of studies. No language restriction was applied. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing salvage systemic therapy (chemotherapy and/or biological therapy) and either another type of salvage systemic therapy, placebo, best supportive care (BSC) or no treatment in patients with gastric and OGJ adenocarcinoma refractory to first-line fluoropyrimidine and platinum-containing chemotherapy. DATA COLLECTION AND ANALYSIS: Two review authors independently performed selection of eligible studies and the primary author extracted study characteristics and outcome data from included studies. We assessed the quality and risk of bias of eligible studies according to the Cochrane Handbook for Systematic Reviews of Interventions. We expressed pooled estimates of effect using hazard ratio (HR) calculated using an inverse variance random-effects model for time-to-event data, and risk ratio (RR) calculated using Mantel-Haenszel random-effects model for binary data. The certainty of evidence was graded using GRADEpro. MAIN RESULTS: We identified 17 RCTs with 5110 participants for inclusion in this review. Tweenty-nine studies are ongoing and twenty studies are awaiting classification. No studies examined the following comparisons: chemotherapy combined with biological therapy versus placebo, BSC or no treatment, chemotherapy combined with biological therapy versus biological therapy, biological therapy versus biological therapy and chemotherapy combined with biological therapy versus chemotherapy combined with biological therapy. Chemotherapy versus placebo, best supportive care or no treatment Chemotherapy probably improves OS (HR = 0.66, 95% CI 0.52 to 0.83, moderate-certainty evidence) based on two studies involving 547 participants and improves PFS (HR = 0.57, 95% CI 0.47 to 0.69, high-certainty evidence) based on one study involving 507 participants over placebo and BSC. Chemotherapy probably increases serious AEs (SAEs) (RR = 1.38, 95% CI 1.20 to 1.59, moderate-certainty evidence) based on one study involving 503 participants. Biological therapy versus placebo, best supportive care or no treatment Biological therapy improves OS (HR = 0.55, 95% CI 0.41 to 0.73, high-certainty evidence) and probably improves PFS (HR = 0.33, 95% CI 0.19 to 0.57, moderate-certainty evidence) over placebo based on three studies involving 781 participants. There is currently insufficient evidence for increased SAEs from biological therapy (RR = 1.14, 95% CI 0.95 to 1.37, low-certainty evidence) based on two studies involving 638 participants. Chemotherapy versus biological therapy This comparison only considered immunotherapy. There is probably no evidence of a difference for OS (HR = 0.82, 95% CI 0.66 to 1.02, moderate-certainty evidence) between chemotherapy and immunotherapy, and immunotherapy probably reduces PFS (HR = 1.27, 95% CI 1.03 to 1.57, moderate-certainty evidence) based on one study involving 395 participants. SAEs may be less frequent with immunotherapy compared to chemotherapy (RR = 0.41, 95% CI 0.30 to 0.57, low-certainty evidence). Chemotherapy combined with biological therapy versus chemotherapy Addition of biological therapy to chemotherapy probably does not improve OS (HR = 0.93, 95% CI 0.83 to 1.04, moderate-certainty evidence) and we are uncertain whether it improves PFS (HR = 0.87, 95% CI 0.74 to 1.02, very low-certainty evidence) based on seven studies involving 2743 participants. We are similarly uncertain whether combined chemotherapy and biological therapy increases SAEs (RR = 1.17, 95% CI 0.95 to 1.44, very low-certainty evidence) based on four studies involving 1618 participants. Chemotherapy versus chemotherapy There is no evidence of a difference for OS and PFS between irinotecan and paclitaxel (HR = 1.13, 95% CI 0.86 to 1.48, low-certainty evidence for OS; HR = 1.14, 95% CI 0.88 to 1.48, low-certainty evidence for PFS) based on one study involving 219 participants. Similarly, there is no evidence to indicate improved OS and PFS from addition of another chemotherapy to docetaxel (HR = 1.05, 95% CI 0.72 to 1.54, low-certainty evidence for OS; HR = 0.75, 95% CI 0.52 to 1.09, low-certainty evidence for PFS) based on two studies involving 121 participants. Grade ≥ 3 neutropenia occurred commonly with both mono- and poly-chemotherapy except for docetaxel-S1 and EOX chemotherapy. AUTHORS' CONCLUSIONS: Survival outcome of patients with advanced gastric and OGJ adenocarcinoma whose disease progressed on first-line fluoropyrimidine and platinum-containing chemotherapy can be improved by chemotherapy and biological therapy. Biological therapy, in particular, achieves this without clear increase in SAEs or QoL impairment. Whether biological therapy is preferred over chemotherapy is still unclear and there is no evidence of a difference for OS outcome, although immunotherapy may be associated with less SAEs. Addition of biological therapy to chemotherapy and poly-chemotherapy are associated with frequent treatment-related toxicity without clear survival benefit.

Pre-treatment serum lactate dehydrogenase as a biomarker in small cell lung cancer.

BACKGROUND: Small cell lung cancer is a rapidly progressive disease with high fatality. No sensitive and specific biomarker to assist in managing this disease exists currently. AIM: Role of pretreatment serum lactate dehydrogenase as a biomarker in small cell lung cancer. METHODS: A hospital-based cancer registry was used to identify eligible patients from 1999 to 2009. Demographic data, lactate dehydrogenase level and clinical outcome of patients were collected for analysis. RESULTS: One hundred and sixty-eight patients were identified: 61% (n = 103) males and 39% (n = 65) females. Majority had extensive stage (67%). High lactate dehydrogenase (≥230 U/L) was present in 60.4% (n = 75); mean reading 260 U/L (range 148-898 U/L) in limited stage and 470 U/L (range 116-5462 U/L) in extensive stage. Extensive stage patients with high lactate dehydrogenase had lower treatment response rate compared to those with normal lactate dehydrogenase (39% vs 79%, P = 0.002); no difference in treatment response was seen among patients with limited stage. High lactate dehydrogenase conferred a worse survival; mean overall survivals in limited and extensive stage were 8.0 and 5.2 months, respectively, in patients with elevated lactate dehydrogenase. Those with normal lactate dehydrogenase had an overall survival of 16.5 and 8.2 months, respectively. The association remained significant after adjustment for age, sex and treatment (HR 1.8, 95% CI 1.16-2.80, P = 0.009). CONCLUSION: High pretreatment lactate dehydrogenase is a prognostic marker of survival in both stages of small cell lung cancer. It is also a predictive marker of response to therapy in extensive stage. Larger prospective studies to validate our findings would be beneficial.

Autoimmune limbic encephalitis with anti-contactin-associated protein-like 2 antibody secondary to pembrolizumab therapy.

Immune checkpoint inhibitors such as Pembrolizumab are used to restore antitumour immune response. It is important to be vigilant of immune mediated adverse events related to such therapy. We report a case of autoimmune limbic encephalitis with Contactin-Associated Protein-like 2 (CASPR2) antibody secondary to Pembrolizumab therapy for metastatic melanoma.

Risk of cumulative toxicity after complete melanoma response with pembrolizumab.

Pembrolizumab is an approved first-line systemic therapy for unresectable metastatic melanoma. Despite the achievement of complete and durable responses in a small subgroup of patients, it is standard practice that pembrolizumab therapy continues beyond complete response. Nevertheless, the incidence of immune-related toxicities gradually increases with continuing pembrolizumab therapy. We report a case highlighting the occurrence of serious induced immune-related adverse events, which were attributed to pembrolizumab in a patient with metastatic melanoma who obtained a complete response (CR) after receiving pembrolizumab for a total of 6.5 months. Although mild pembrolizumab-related toxicity persists, the patient remains disease-free 5.5 months after discontinuation of pembrolizumab. Accordingly, we believe that cessation of pembrolizumab should be considered in patients who achieve a CR because of the ongoing risk of toxicity with extended pembrolizumab administration.

Vedolizumab: a novel treatment for ipilimumab-induced colitis.

Use of the immune checkpoint inhibitors, ipilimumab and nivolumab, has revolutionised treatment in patients with metastatic melanoma. However, these drugs can cause an autoimmune enterocolitis, with diarrhoea as the presenting symptom. This is conventionally managed by prompt institution of corticosteroid therapy if moderate diarrhoea (3-6 times/day; grade 2) is present for >5 days or if diarrhoea is severe (>6 times/day; grade 3). We report a case of steroid-dependent ipilimumab-induced colitis successfully treated with vedolizumab (an inhibitor of memory T-cell trafficking to the gut), after which complete withdrawal of corticosteroid was achieved. Hence, vedolizumab warrants further evaluation as a potential novel treatment of ipilimumab-induced colitis.

Fundamental concerns of women living with HIV around the implementation of Option B+.

INTRODUCTION: In 2011, the Global Plan towards the Elimination of New HIV Infections among Children by 2015 and Keeping Their Mothers Alive was launched to scale up efforts to comprehensively end vertical HIV transmission and support mothers living with HIV in remaining healthy. Amidst excitement around using treatment as prevention, Malawi's Ministry of Health conceived Option B+, a strategy used to prevent vertical transmission by initiating all pregnant and breastfeeding women living with HIV on lifelong antiretroviral therapy, irrespective of CD4 count. In 2013, for programmatic and operational reasons, the WHO officially recommended Option B+ to countries with generalized epidemics, limited access to CD4 testing, limited partner testing, long breastfeeding duration or high fertility rates. DISCUSSION: While acknowledging the opportunity to increase treatment access globally and its potential, this commentary reviews the concerns of women living with HIV about human rights, community-based support and other barriers to service uptake and retention in the Option B+ context. Option B+ intensifies many of the pre-existing challenges of HIV prevention and treatment programmes. As women seek comprehensive services to prevent vertical transmission, they can experience various human rights violations, including lack of informed consent, involuntary or coercive HIV testing, limited treatment options, termination of pregnancy or coerced sterilization and pressure to start treatment. Yet, peer and community support strategies can promote treatment readiness, uptake, adherence and lifelong retention in care; reduce stigma and discrimination; and mitigate potential violence stemming from HIV disclosure. Ensuring available and accessible quality care, offering food support and improving linkages to care could increase service uptake and retention. With the heightened focus on interventions to reach pregnant and breastfeeding women living with HIV, a parallel increase in vigilance to secure their health and rights is critical. CONCLUSION: The authors conclude that real progress towards reducing vertical transmission and achieving viral load suppression can only be made by upholding the human rights of women living with HIV, investing in community-based responses, and ensuring universal access to quality healthcare. Only then will the opportunity of accessing lifelong treatment result in improving the health, dignity and lives of women living with HIV, their children and families.

Can maintenance trastuzumab be stopped in patients with HER2-positive metastatic breast cancer?

Trastuzumab has significantly improved the median survival of patients with HER2-positive breast cancer. In metastatic disease, maintenance trastuzumab is usually given after tumour response has been achieved with the combination of chemotherapy and trastuzumab, with the aim of prolonging time to disease progression. We report a case where a durable complete response (CR) was achieved without maintenance trastuzumab. In the absence of consensus guidelines, it is difficult to recommend which HER2-positive patients with metastatic breast cancer after CR will benefit from withdrawing maintenance trastuzumab therapy and when this could be considered.

From patient to person: the need for an 'HIV trajectories' perspective in the delivery of prevention of mother-to-child-transmission services.

Accelerated efforts to end vertical HIV transmission have resulted in a 52% decrease in new infections among children since 2001. However, current approaches to prevent mother-to-child-transmission (PMTCT) assume a linearity and universality. These insufficiently guide clinicians and programmes toward interventions that comprehensively address the varying and changing needs of clients. This results in high levels of loss-to-follow-up at each step of the PMTCT cascade. Current PMTCT approaches must be adapted to respond to the different and complex realities of women, children and families affected by HIV. Drawing on the concept of an 'HIV trajectories,' we screened peer-reviewed literature for promising PMTCT approaches and selected 13 articles for qualitative review when the described intervention involved more than a biomedical approach to PMTCT and mother-child HIV treatment and care. Our qualitative analysis revealed that interventions which integrated elements of the 'HIV trajectories' perspective and built on people living with HIV support/network, community health worker, primary healthcare and early childhood development platforms were successful because they recognized that HIV is an illness, experienced, moderated and managed by numerous factors beyond biomedical interventions alone.On the basis of this review, we call for the adoption of an 'HIV trajectories' perspective that can help assess the comprehensiveness of care provided to women, children and families affected by HIV and can inform the planning and delivery of HIV and related services so that they more adequately respond to the varying needs of clients on different 'HIV trajectories'.

Community and service provider views to inform the 2013 WHO consolidated antiretroviral guidelines: key findings and lessons learnt.

OBJECTIVE: The objective was to evaluate community and healthcare worker (HCW) values and preferences on key topics to inform the development of the 2013 WHO consolidated guidelines for antiretroviral therapy in low and middle income countries. DESIGN: Cross-sectional e-survey and e-forum discussion; focus group discussions (FGDs) METHODS: : Data were collected on community perspectives regarding a range of potential clinical and operational recommendations in the 2013 guidelines between November 2012 and January 2013 through an e-survey (n = 1088) and e-forum (n = 955). Additional FGDs were held with people living with HIV (PLHIV) in Malawi and Uganda (n = 88) on antiretroviral therapy (ART) use among pregnant women. Two surveys were also undertaken on similar topics covered in the e-survey for health care workers caring for adults (n = 98) and children (n = 348). RESULTS: There were 1088 e-survey respondents from 117 countries: of whom 37.7% (298/791) were females, 49.9% (431/864) PLHIV, and 20.9% (174/831) from low-income countries. The proportion of e-survey respondents who supported raising the CD4 T-cell threshold for ART initiation in adults from 350 to 500 cells/µl was 51.0% (355/696), and regardless of CD4 T-cell count for all pregnant females 89.8% (607/676), HIV serodiscordant partners 71.9% (486/676), and all children on diagnosis of infection 47.4% (212/447). E-survey respondents strongly supported discontinuing use of stavudine (72.7%, 416/572), task-shifting/sharing from doctors to nurses (75.2%, 275/365) and from nurses to community health workers (71.1%, 261/367) as strategies to expand access to HIV testing, care, and treatment. Focus group discussion respondents identified service capacity, and social and legal concerns as key considerations influencing the decisions of women living with HIV to continue ART after the risk of vertical transmission has passed. Key lessons learnt in these consultations included the need for piloting and validation of questions; sufficient time to adequately disseminate the survey; and consideration of using FGDs and mobile phone technology to improve participation of people with limited internet access. CONCLUSION: Community participation in guideline development processes is important to ensure that their perspectives are considered in the resulting recommendations. Communities should be actively involved in the adaptation, implementation, and accountability processes related to the guidelines.

Community voices: barriers and opportunities for programmes to successfully prevent vertical transmission of HIV identified through consultations among people living with HIV.

INTRODUCTION: In 2010, two global networks of people living with HIV, the International Community of Women Living with HIV (ICW Global) and the Global Network of People living with HIV (GNP+) were invited to review a draft strategic framework for the global scale up of prevention of vertical transmission (PVT) through the primary prevention of HIV and the prevention of unintended pregnancies among women living with HIV. In order to ensure recommendations were based on expressed needs of people living with HIV, GNP+ and ICW Global undertook a consultation amongst people living with HIV which highlighted both facilitators and barriers to prevention services. This commentary summarizes the results of that consultation. DISCUSSION: The consultation was comprised of an online consultation (moderated chat-forum with 36 participants from 16 countries), an anonymous online e-survey (601 respondents from 58 countries), and focus-group discussions with people living with HIV in Jamaica (27 participants). The consultation highlighted the discrepancies across regions with respect to access to essential packages of PVT services. However, the consultation participants also identified common barriers to access, including a lack of trustworthy sources of information, service providers' attitudes, and gender-based violence. In addition, participant responses revealed common facilitators of access, including quality counselling on reproductive choices, male involvement, and decentralized services. CONCLUSIONS: The consultation provided some understanding and insight into the participants' experiences with and recommendations for PVT strategies. Participants agreed that successful, comprehensive PVT programming require greater efforts to both prevent primary HIV infection among young women and girls and, in particular, targeted efforts to ensure that women living with HIV and their partners are supported to avoid unintended pregnancies and to have safe, healthy pregnancies instead. In addition to providing the insights into prevention services discussed above, the consultation served as a valuable example of the meaningful involvement of people living with HIV in programming and implementation to ensure that programs are tailored to individuals' needs and to circumvent rights abuses within those settings.

Can interactive skills-based seminars with standardized patients enhance clinicians' prevention skills? Measuring the impact of a CME program.

OBJECTIVE: Communication skills are crucial for high-risk behavior screening and counseling. Practicing physicians have limited opportunities to improve these skills. This paper assesses the impact of a continuing medical education (CME) program for Student Health Center clinicians that targeted communication skills, screening practices and patient satisfaction. METHODS: Program evaluation included pre- and post-objective structured clinical examinations (OSCE's), chart review, and provider and patient satisfaction surveys. Data were analyzed using paired t-tests and ranked sum tests. RESULTS: OSCE scores (n=15) revealed significant improvements in communication skills overall (p=0.004) and within specific domains (data gathering: p=0.003; rapport building: p=0.01; patient education: p=0.02), but no change in case-specific knowledge (p=0.1). Participants (n=14) reported high satisfaction with program methods (mean=4.6/5) and content (mean=4.7/5), 70% planning to alter their clinical practice. Chart audits (pre=96, post=103) showed increased screening for smoking (RR 1.65, p=0.03), depressed mood (RR 1.40, p=0.04), anhedonia (RR 1.47, p=0.01), sexual activity (RR 1.73, p=0.002) and drinking (RR 1.77, p=0.04). Sampling of satisfaction among participants' patients (pre n=689, post n=383) detected no increase in already high baseline satisfaction. CONCLUSION: This curriculum improved clinicians' relevant skills and screening behavior. PRACTICE IMPLICATIONS: Skills-oriented CME can improve clinicians' communication skills and screening and counseling practices.

Can unannounced standardized patients assess professionalism and communication skills in the emergency department?

OBJECTIVES: The authors piloted unannounced standardized patients (USPs) in an emergency medicine (EM) residency to test feasibility, acceptability, and performance assessment of professionalism and communication skills. METHODS: Fifteen postgraduate year (PGY)-2 EM residents were scheduled to be visited by two USPs while working in the emergency department (ED). Multidisciplinary support was utilized to ensure successful USP introduction. Scores (% well done) were calculated for communication and professionalism skills using a 26-item, behaviorally anchored checklist. Residents' attitudes toward USPs and USP detection were also surveyed. RESULTS: Of 27 USP encounters attempted, 17 (62%) were successfully completed. The detection rate was 44%. Eighty-three percent of residents who encountered a USP felt that the encounter did not hinder daily practice and did not make them uncomfortable (86%) or suspicious of patients (71%). Overall, residents received a mean score of 60% for communication items rated "well done" (SD +/- 28%, range = 23%-100%) and 53% of professionalism items "well done" (SD +/- 20%, range = 23%-85%). Residents' communication skills were weakest for patient education and counseling (mean = 43%, SD +/- 31%), compared with information gathering (68%, SD +/- 36% and relationship development (62%, SD +/- 32%). Scores of residents who detected USPs did not differ from those who had not. CONCLUSIONS: Implementing USPs in the ED is feasible and acceptable to staff. The unpredictability of the ED, specifically resident schedules, accounted for most incomplete encounters. USPs may represent a new way to assess real-time resident physician performance without the need for faculty resources or the bias introduced by direct observation.

A sulfated, phosphorylated 7 kDa secreted peptide characterized by direct analysis of cell culture media.

An unusual sulfotyrosine-, phosphoserine-containing motif was mapped on a differentially post-translationally modified 60 residue antimicrobial neuroendocrine peptide called chrombacin. The study was performed by high resolution FT MS using complementary fragmentation techniques. The peptide was analyzed at low levels directly from cell culture media in contrast to previous reports that required extensive purification and proteolytic digestion. The sulfation site was not previously described nor predicted by informatic analysis of the peptide's precursor sequence.

Medical training in school-based health centers: a collaboration among five medical schools.

School-based health centers (SBHCs) have tremendous untapped potential as models for learning about systems-based care of vulnerable children. SBHCs aim to provide comprehensive, community-based primary health care to primary and secondary schoolchildren who might not otherwise have ready access to that care. The staffing at SBHCs is multidisciplinary, including various combinations of nurse practitioners, physicians, dentists, nutritionists, and mental health providers. Although this unique environment provides obvious advantages to children and their families, medical students and residents receive little or no preparation for this type of practice. To address these deficiencies in medical education, five downstate New York state medical schools, funded by the New York State Department of Health, collaborated to define, develop, implement, and evaluate curricula that expose health professions students and residents to SBHCs. The schools identified core competencies and developed a comprehensive training model for the project, including clinical experiences, didactic sessions, and community service opportunities, and they developed goals, objectives, and learning materials for each competency for all types and levels of learners. Each school has implemented a wide range of learning activities based on the competencies. In this paper, the authors describe the development of the collaboration and illustrate the process undertaken to implement new curricula, including considerations made to address institutional needs, curricula development, and incorporation into existing curricula. In addition, they discuss the lessons learned from conducting this collaborative effort among medical schools, with the goal of providing guidance to establish effective cross-disciplinary curricula that address newly defined competencies.

Effects of corneal thickness, corneal curvature, and intraocular pressure level on Goldmann applanation tonometry and dynamic contour tonometry.

PURPOSE: To compare the measurements of intraocular pressure (IOP) with Goldmann applanation tonometry (GAT) and dynamic contour tonometry (DCT) and the effects of central corneal thickness (CCT), corneal curvature, and level of IOP on these methods. DESIGN: Cross-sectional population-based study. PARTICIPANTS: From the Los Angeles Latino Eye Study, 2157 participants of primarily Mexican ancestry. METHODS: Average GAT measurements were compared to DCT, and both were examined with respect to CCT (< or =500, 501-550, 551-600, >600 microns), corneal curvature (<42, 42-46, >46 diopters), and level of IOP (0-10, 11-20, >20 mmHg). MAIN OUTCOME MEASURES: Mean GAT and DCT IOP levels were compared for the entire population, and then trends for the CCT, curvature, and IOP groupings were analyzed. The magnitude of the difference of GAT minus DCT was compared for these different strata, with special attention to a difference of +/- 3 mmHg or greater, which was defined as clinically significant. RESULTS: Mean IOP for the entire population by GAT was significantly lower (14.4+/-3.2 mmHg) compared with DCT (16.0+/-3.6; P<0.0001). Both GAT and DCT IOP levels were lowest for thin CCT and increased stepwise with increasing CCT, but this difference was more pronounced with GAT than DCT (P<0.0001 and P = 0.0012, respectively). The difference between GAT and DCT was largest for thin CCT and decreased for thicker CCT (P<0.0001). After adjusting for CCT, the corneal curvature affected IOP measured by DCT (P = 0.02) but not GAT (P = 0.3) such that mean DCT IOP increased with increasing corneal curvature. After adjusting for the CCT effect on IOP and stratifying by DCT IOP groups, the greatest difference between GAT and DCT was seen in the lowest IOP group (3.55+/-3.1), became negative in the intermediate group (-1.86+/-2.60), and was most negative in the highest IOP group (-3.88+/-3.3; P<0.0001). CONCLUSIONS: Intraocular pressure measured by GAT was consistently lower when compared with DCT, and this difference was greatest with thinner CCT. Dynamic contour tonometry was also less affected by variations in CCT. Corneal curvature affected IOP measurements with DCT but not GAT, but this effect was less than the CCT effect on GAT. Goldmann applanation tonometry tended to underestimate IOP at higher levels and overestimate it at lower IOP levels when compared to DCT.