Hjalmar Lagast - Academia.edu (original) (raw)

Papers by Hjalmar Lagast

Additional file 1. ESSENCE individual baseline characteristics of the vehicle group. Contains ind... more Additional file 1. ESSENCE individual baseline characteristics of the vehicle group. Contains individual de-identified data of patients who were randomly assigned to the vehicle group in the current study.

Journal of Investigative Dermatology, 2018

Psoriasis is a common dermatologic condition and autoimmune disease characterized by red, itchy, ... more Psoriasis is a common dermatologic condition and autoimmune disease characterized by red, itchy, and scaly patches of skin due to overgrowth of skin cells. This retrospective metaanalysis evaluates the association between hospital teaching status and psoriasis outcomes by comparing the number of discharges, length of stay (LOS), and charges between teaching and non-teaching hospitals. Using ICD-9-CM codes for psoriasis, all admissions with a primary diagnosis of psoriasis between 1997-2014 were identified from the Nationwide Inpatient Sample database. Hospital admission information including LOS, total charges, and number of discharges were extracted for teaching and non-teaching hospitals. Statistical significance was determined by the z-test (p¼0.05). There were 17,107 discharges identified with a primary diagnosis of psoriasis from 1997-2014. There were more discharges at teaching hospitals (N ¼ 10,204) in comparison to the number of discharges in non-teaching hospitals (N ¼ 6,903), with statistically significant differences in 11 of the 18 years studied. The average LOS (days) was found to be longer in teaching hospitals (5.91) than in non-teaching hospitals (5.44), and there were statistically significant differences in 1999-2001, 2004, and 2012. Total charges were also greater in teaching hospitals ($19,043.33) versus non-teaching hospitals ($16,320.06), and there were statistically significant differences in 1997, 1999, 2001, and 2012. In conclusion, more psoriasis discharges occured at teaching hospitals. The increase in total charges at teaching hospitals may be due to many factors such as an increased LOS, complication rates, and medical complexity. Some limitations to this study include not taking comorbidities into consideration, and not exploring the relationship of hospital teaching status to other hospital characteristics such as its technology capabilities, number of residents, and volume of cases. By comparing the data provided in teaching and non-teaching hospitals, policymakers, insurers, and patients can make more knowledgeable decisions based on the best type of hospitals for psoriasis patients.

Applied Microbiology and Biotechnology, 1987

In 1985 the European Federation of Biotechnology accepted a classification of microorganisms acco... more In 1985 the European Federation of Biotechnology accepted a classification of microorganisms according to their pathogenicity which included the EFB group E (environmental risk) m. These microorganisms are more dangerous for the fauna and flora in the environment than for laboratory workers and operators; economic losses however may be caused by escaping microorganisms. Because several of these microorganisms are of biotechnological importance their classification and corresponding levels of containment need to be established L21. As far as plants are concerned three classes with increasing risk for the environment can be discerned within the group EFB E. The lowest class of pathogens for plants is EFB Ep 1 followed by the medium class EFB Ep 2 and the highest class EFB Ep 3. None of these microorganisms are known to be harmful to humans and animals. In the following table the definitions of the three classes EFB Ep 1--3 are shown. Potential large-scale users of pathogens of plants should consult their national plant protection authority and agree the correct classification in EFB Ep 1, Ep 2 or Ep 3, so that an appropriate level of containment can be applied in their biotechnological work.

Cancer Chemotherapy and Selective Drug Development, 1984

It has been shown since 1966 (1) that infection is related to the absolute level of granulocytes.... more It has been shown since 1966 (1) that infection is related to the absolute level of granulocytes. When the granulocyte count is below 100/µ 1, the patient is at the greatest risk of severe infections and gram-negative bacteremias are common (2).

Additional file 1. Patient Survey. Copy of patient survey

Journal of Investigative Dermatology, 2018

One of the clinical challenges in melanoma is the early identification of patients with intermedi... more One of the clinical challenges in melanoma is the early identification of patients with intermediary thickness melanomas who will go on to develop progressive disease. We created a clinically well-characterized cohort of 53 thin intermediary thickness melanomas (Breslow thickness 1-2 mm) including tumors from patients with localized disease (N¼26) and melanomas from patients with regional spreading (N¼27). Eleven of the patients experienced recurrence of disease after treatment. We hypothesized that melanomas from patients with regional metastases or recurrence would leave a distinct molecular signature. Gene expression was measured in 740 known cancer genes using the NanoString PanCancer pathways panel. Tumor DNA was analyzed for BRAF and NRAS mutations and found in 69.8% and 15.1% of the tumors, respectively. We found the expression of the ubiquitin ligase Deltex E3 (DTX3) to be significantly upregulated in melanomas from patients with recurrence (p¼0.00001, FDR DTX3 modulates the DNA damage response and has not previously been associated with recurrence. Other interesting genes included Frizzled class receptor 3 (FZD3) (p¼0.00004, FDR¼0.06, log2 fc 0.52AE0.12), IL-1 (p¼0.0001, FDR¼0.06, log2 fc 2.22AE0.52) and leptin (p¼0.00003, FDR¼0.06, log2 fc 1.23AE0.27). IL-1b is a cytokine that is secreted by melanoma cells and has been suggested to promote tumor growth and metastasis. Leptin is a metabolic hormone produced by melanoma cells and has been shown to activate the MAPK pathway. None of these genes have previously been associated with recurrence and we conclude that intermediary thickness melanomas from patients with recurrence might have a distinct molecular signature.

Medecine Et Hygiene, 1981

SCOPUS: NotDefined.jinfo:eu-repo/semantics/publishe

American Journal of Hypertension, 2003

Antimicrobial Agents and Chemotherapy, 1983

Clinical and Experimental Nephrology, 2019

Background Fabry disease is a progressive X-linked lysosomal disorder. In this subgroup analysis ... more Background Fabry disease is a progressive X-linked lysosomal disorder. In this subgroup analysis of the global phase III ATTRACT study, the efficacy and safety of oral migalastat, a pharmacologic chaperone, were investigated in Japanese patients with Fabry disease. Methods Patients were randomly assigned to receive migalastat (150 mg every other day) or to continue biweekly enzyme replacement therapy infusions (ERT; agalsidase alfa 0.2 mg/kg or agalsidase beta 1.0 mg/kg) for 18 months followed by a 12-month open-label extension during which all patients received migalastat. End points included glomerular filtration rate (estimated and measured), left ventricular mass index (LVMi), composite clinical outcomes, leukocyte alpha-galactosidase A activity, plasma globotriaosylsphingosine (lyso-Gb3), and safety. Results Data from 7 Japanese patients (migalastat, 5; ERT, 2), mean age 55 years, with high disease burden, were analyzed. All patients in the migalastat group completed the open-l...

Orphanet Journal of Rare Diseases, 2020

Background Little information is available regarding the burden of living with and managing epide... more Background Little information is available regarding the burden of living with and managing epidermolysis bullosa, including the distinct challenges faced by patients with different disease types/subtypes. Methods A 90-question/item survey was developed to collect demographics, diagnostic data, management practices, and burden of illness information for patients with epidermolysis bullosa living in the United States. Recruitment was conducted via email and social media in partnership with epidermolysis bullosa patient advocacy organizations in the United States, and the survey was conducted via telephone interview by a third-party health research firm. Respondents aged ≥ 18 years with a confirmed diagnosis of epidermolysis bullosa or caring for a patient with a confirmed diagnosis of epidermolysis bullosa were eligible to participate in the survey. Results In total, 156 responses were received from patients (n = 63) and caregivers (n = 93) representing the epidermolysis bullosa type...

Additional file 2. Patient Enrollment Map. US map showing number of enrolled patients per state.

Molecular Genetics and Metabolism

Molecular Genetics and Metabolism

Journal of Investigative Dermatology

The present invention relates to compositions for treating prepubertal males of adolescent age wi... more The present invention relates to compositions for treating prepubertal males of adolescent age with insufficient testosterone production using a hydroalcoholic testosterone gel formulation that provides, among other things, a desirable pharmacokinetic hormone profile, and methods of treating said adolescent males.

Endocrine Practice, 2015

Hypoparathyroidism is characterized by inadequate parathyroid hormone (PTH), resulting in hypocal... more Hypoparathyroidism is characterized by inadequate parathyroid hormone (PTH), resulting in hypocalcemia, hyperphosphatemia, and bone abnormalities. Adults with hypoparathyroidism treated with recombinant human PTH, rhPTH(1-84), in the 24-week, phase III REPLACE study maintained serum calcium despite reductions in oral calcium and active vitamin D. This study assessed the long-term efficacy and safety of rhPTH(1-84) for hypoparathyroidism. This was a 24-week, open-label, flexible-dose extension study of REPLACE (REPEAT) conducted in 3 outpatient centers in Hungary. Patients who previously completed or enrolled in REPLACE received 50 μg/day rhPTH(1-84), escalated to 75 and then to 100 μg/day, if needed, to reduce active vitamin D and oral calcium. The primary endpoint was ≥50% reduction in oral calcium (or ≤500 mg/day) and active vitamin D (or calcitriol ≤0.25 μg/day or alfacalcidol ≤0.50 μg/day) with normocalcemia. 24 patients (n=16 previously treated with rhPTH[1-84]; n=8 rhPTH[1-84]-naive) enrolled; all completed the study. At Week 24, 75% of patients (95% CI, 53.3%-90.2%) achieved the study endpoint; 58% eliminated oral calcium and active vitamin D. Urinary calcium, serum phosphate, and calcium × phosphate product decreased by Week 24. Mean serum bone turnover markers increased with rhPTH(1-84). Treatment-emergent adverse events (AEs) were reported by 92% of patients. No serious AEs occurred. This study, using a simplified treatment algorithm intended to better mimic typical clinical practice, demonstrated the extended efficacy and safety of rhPTH(1-84) in patients with hypoparathyroidism and confirmed the REPLACE findings. Sustained rhPTH(1-84) efficacy up to 48 weeks was observed despite treatment interruption between studies.

Additional file 1. ESSENCE individual baseline characteristics of the vehicle group. Contains ind... more Additional file 1. ESSENCE individual baseline characteristics of the vehicle group. Contains individual de-identified data of patients who were randomly assigned to the vehicle group in the current study.

Journal of Investigative Dermatology, 2018

Psoriasis is a common dermatologic condition and autoimmune disease characterized by red, itchy, ... more Psoriasis is a common dermatologic condition and autoimmune disease characterized by red, itchy, and scaly patches of skin due to overgrowth of skin cells. This retrospective metaanalysis evaluates the association between hospital teaching status and psoriasis outcomes by comparing the number of discharges, length of stay (LOS), and charges between teaching and non-teaching hospitals. Using ICD-9-CM codes for psoriasis, all admissions with a primary diagnosis of psoriasis between 1997-2014 were identified from the Nationwide Inpatient Sample database. Hospital admission information including LOS, total charges, and number of discharges were extracted for teaching and non-teaching hospitals. Statistical significance was determined by the z-test (p¼0.05). There were 17,107 discharges identified with a primary diagnosis of psoriasis from 1997-2014. There were more discharges at teaching hospitals (N ¼ 10,204) in comparison to the number of discharges in non-teaching hospitals (N ¼ 6,903), with statistically significant differences in 11 of the 18 years studied. The average LOS (days) was found to be longer in teaching hospitals (5.91) than in non-teaching hospitals (5.44), and there were statistically significant differences in 1999-2001, 2004, and 2012. Total charges were also greater in teaching hospitals ($19,043.33) versus non-teaching hospitals ($16,320.06), and there were statistically significant differences in 1997, 1999, 2001, and 2012. In conclusion, more psoriasis discharges occured at teaching hospitals. The increase in total charges at teaching hospitals may be due to many factors such as an increased LOS, complication rates, and medical complexity. Some limitations to this study include not taking comorbidities into consideration, and not exploring the relationship of hospital teaching status to other hospital characteristics such as its technology capabilities, number of residents, and volume of cases. By comparing the data provided in teaching and non-teaching hospitals, policymakers, insurers, and patients can make more knowledgeable decisions based on the best type of hospitals for psoriasis patients.

Applied Microbiology and Biotechnology, 1987

In 1985 the European Federation of Biotechnology accepted a classification of microorganisms acco... more In 1985 the European Federation of Biotechnology accepted a classification of microorganisms according to their pathogenicity which included the EFB group E (environmental risk) m. These microorganisms are more dangerous for the fauna and flora in the environment than for laboratory workers and operators; economic losses however may be caused by escaping microorganisms. Because several of these microorganisms are of biotechnological importance their classification and corresponding levels of containment need to be established L21. As far as plants are concerned three classes with increasing risk for the environment can be discerned within the group EFB E. The lowest class of pathogens for plants is EFB Ep 1 followed by the medium class EFB Ep 2 and the highest class EFB Ep 3. None of these microorganisms are known to be harmful to humans and animals. In the following table the definitions of the three classes EFB Ep 1--3 are shown. Potential large-scale users of pathogens of plants should consult their national plant protection authority and agree the correct classification in EFB Ep 1, Ep 2 or Ep 3, so that an appropriate level of containment can be applied in their biotechnological work.

Cancer Chemotherapy and Selective Drug Development, 1984

It has been shown since 1966 (1) that infection is related to the absolute level of granulocytes.... more It has been shown since 1966 (1) that infection is related to the absolute level of granulocytes. When the granulocyte count is below 100/µ 1, the patient is at the greatest risk of severe infections and gram-negative bacteremias are common (2).

Additional file 1. Patient Survey. Copy of patient survey

Journal of Investigative Dermatology, 2018

One of the clinical challenges in melanoma is the early identification of patients with intermedi... more One of the clinical challenges in melanoma is the early identification of patients with intermediary thickness melanomas who will go on to develop progressive disease. We created a clinically well-characterized cohort of 53 thin intermediary thickness melanomas (Breslow thickness 1-2 mm) including tumors from patients with localized disease (N¼26) and melanomas from patients with regional spreading (N¼27). Eleven of the patients experienced recurrence of disease after treatment. We hypothesized that melanomas from patients with regional metastases or recurrence would leave a distinct molecular signature. Gene expression was measured in 740 known cancer genes using the NanoString PanCancer pathways panel. Tumor DNA was analyzed for BRAF and NRAS mutations and found in 69.8% and 15.1% of the tumors, respectively. We found the expression of the ubiquitin ligase Deltex E3 (DTX3) to be significantly upregulated in melanomas from patients with recurrence (p¼0.00001, FDR DTX3 modulates the DNA damage response and has not previously been associated with recurrence. Other interesting genes included Frizzled class receptor 3 (FZD3) (p¼0.00004, FDR¼0.06, log2 fc 0.52AE0.12), IL-1 (p¼0.0001, FDR¼0.06, log2 fc 2.22AE0.52) and leptin (p¼0.00003, FDR¼0.06, log2 fc 1.23AE0.27). IL-1b is a cytokine that is secreted by melanoma cells and has been suggested to promote tumor growth and metastasis. Leptin is a metabolic hormone produced by melanoma cells and has been shown to activate the MAPK pathway. None of these genes have previously been associated with recurrence and we conclude that intermediary thickness melanomas from patients with recurrence might have a distinct molecular signature.

Medecine Et Hygiene, 1981

SCOPUS: NotDefined.jinfo:eu-repo/semantics/publishe

American Journal of Hypertension, 2003

Antimicrobial Agents and Chemotherapy, 1983

Clinical and Experimental Nephrology, 2019

Background Fabry disease is a progressive X-linked lysosomal disorder. In this subgroup analysis ... more Background Fabry disease is a progressive X-linked lysosomal disorder. In this subgroup analysis of the global phase III ATTRACT study, the efficacy and safety of oral migalastat, a pharmacologic chaperone, were investigated in Japanese patients with Fabry disease. Methods Patients were randomly assigned to receive migalastat (150 mg every other day) or to continue biweekly enzyme replacement therapy infusions (ERT; agalsidase alfa 0.2 mg/kg or agalsidase beta 1.0 mg/kg) for 18 months followed by a 12-month open-label extension during which all patients received migalastat. End points included glomerular filtration rate (estimated and measured), left ventricular mass index (LVMi), composite clinical outcomes, leukocyte alpha-galactosidase A activity, plasma globotriaosylsphingosine (lyso-Gb3), and safety. Results Data from 7 Japanese patients (migalastat, 5; ERT, 2), mean age 55 years, with high disease burden, were analyzed. All patients in the migalastat group completed the open-l...

Orphanet Journal of Rare Diseases, 2020

Background Little information is available regarding the burden of living with and managing epide... more Background Little information is available regarding the burden of living with and managing epidermolysis bullosa, including the distinct challenges faced by patients with different disease types/subtypes. Methods A 90-question/item survey was developed to collect demographics, diagnostic data, management practices, and burden of illness information for patients with epidermolysis bullosa living in the United States. Recruitment was conducted via email and social media in partnership with epidermolysis bullosa patient advocacy organizations in the United States, and the survey was conducted via telephone interview by a third-party health research firm. Respondents aged ≥ 18 years with a confirmed diagnosis of epidermolysis bullosa or caring for a patient with a confirmed diagnosis of epidermolysis bullosa were eligible to participate in the survey. Results In total, 156 responses were received from patients (n = 63) and caregivers (n = 93) representing the epidermolysis bullosa type...

Additional file 2. Patient Enrollment Map. US map showing number of enrolled patients per state.

Molecular Genetics and Metabolism

Molecular Genetics and Metabolism

Journal of Investigative Dermatology

The present invention relates to compositions for treating prepubertal males of adolescent age wi... more The present invention relates to compositions for treating prepubertal males of adolescent age with insufficient testosterone production using a hydroalcoholic testosterone gel formulation that provides, among other things, a desirable pharmacokinetic hormone profile, and methods of treating said adolescent males.

Endocrine Practice, 2015

Hypoparathyroidism is characterized by inadequate parathyroid hormone (PTH), resulting in hypocal... more Hypoparathyroidism is characterized by inadequate parathyroid hormone (PTH), resulting in hypocalcemia, hyperphosphatemia, and bone abnormalities. Adults with hypoparathyroidism treated with recombinant human PTH, rhPTH(1-84), in the 24-week, phase III REPLACE study maintained serum calcium despite reductions in oral calcium and active vitamin D. This study assessed the long-term efficacy and safety of rhPTH(1-84) for hypoparathyroidism. This was a 24-week, open-label, flexible-dose extension study of REPLACE (REPEAT) conducted in 3 outpatient centers in Hungary. Patients who previously completed or enrolled in REPLACE received 50 μg/day rhPTH(1-84), escalated to 75 and then to 100 μg/day, if needed, to reduce active vitamin D and oral calcium. The primary endpoint was ≥50% reduction in oral calcium (or ≤500 mg/day) and active vitamin D (or calcitriol ≤0.25 μg/day or alfacalcidol ≤0.50 μg/day) with normocalcemia. 24 patients (n=16 previously treated with rhPTH[1-84]; n=8 rhPTH[1-84]-naive) enrolled; all completed the study. At Week 24, 75% of patients (95% CI, 53.3%-90.2%) achieved the study endpoint; 58% eliminated oral calcium and active vitamin D. Urinary calcium, serum phosphate, and calcium × phosphate product decreased by Week 24. Mean serum bone turnover markers increased with rhPTH(1-84). Treatment-emergent adverse events (AEs) were reported by 92% of patients. No serious AEs occurred. This study, using a simplified treatment algorithm intended to better mimic typical clinical practice, demonstrated the extended efficacy and safety of rhPTH(1-84) in patients with hypoparathyroidism and confirmed the REPLACE findings. Sustained rhPTH(1-84) efficacy up to 48 weeks was observed despite treatment interruption between studies.