Dr. Joseph  Maximiek  Dmd image

Dr. Joseph Maximiek Dmd

375 Martzville Rd
Berwick PA 18603
570 525-5051
Medical School: Other - Unknown
Accepts Medicare: No
Participates In eRX: No
Participates In PQRS: No
Participates In EHR: No
License #: DS021225L
NPI: 1508911462
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Germline Variants in Targeted Tumor Sequencing Using Matched Normal DNA. - JAMA oncology
Tumor genetic sequencing identifies potentially targetable genetic alterations with therapeutic implications. Analysis has concentrated on detecting tumor-specific variants, but recognition of germline variants may prove valuable as well.To estimate the burden of germline variants identified through routine clinical tumor sequencing.Patients with advanced cancer diagnoses eligible for studies of targeted agents at Memorial Sloan Kettering Cancer Center are offered tumor-normal sequencing with MSK-IMPACT, a 341-gene panel. We surveyed the germline variants seen in 187 overlapping genes with Mendelian disease associations in 1566 patients who had undergone tumor profiling between March and October 2014.The number of presumed pathogenic germline variants (PPGVs) and variants of uncertain significance per person in 187 genes associated with single-gene disorders and the proportions of individuals with PPGVs in clinically relevant gene subsets, in genes consistent with known tumor phenotypes, and in genes with evidence of second somatic hits in their tumors.The mean age of the 1566 patients was 58 years, and 54% were women. Presumed pathogenic germline variants in known Mendelian disease-associated genes were identified in 246 of 1566 patients (15.7%; 95% CI, 14.0%-17.6%), including 198 individuals with mutations in genes associated with cancer susceptibility. Germline findings in cancer susceptibility genes were concordant with the individual's cancer type in only 81 of 198 cases (40.9%; 95% CI, 34.3%-47.9%). In individuals with PPGVs retained in the tumor, somatic alteration of the other allele was seen in 39 of 182 cases (21.4%; 95% CI, 16.1%-28.0%), of which 13 cases did not show a known correlation of the germline mutation and a known syndrome. Mutations in non-cancer-related Mendelian disease genes were seen in 55 of 1566 cases (3.5%; 95% CI, 27.1%-45.4%). Almost every individual had more than 1 variant of uncertain significance (1565 of 1566 patients; 99.9%; 95% CI, 99.6%-99.9%).Germline variants are common in individuals undergoing tumor-normal sequencing and may reveal otherwise unsuspected syndromic associations.
HIV-1-negative female sex workers sustain high cervical IFNÉ›, low immune activation, and low expression of HIV-1-required host genes. - Mucosal immunology
Sex workers practicing in high HIV endemic areas have been extensively targeted to test anti-HIV prophylactic strategies. We hypothesize that in women with high levels of genital exposure to semen changes in cervico-vaginal mucosal and/or systemic immune activation will contribute to a decreased susceptibility to HIV-1 infection. To address this question, we assessed sexual activity and immune activation status (in peripheral blood), as well as cellular infiltrates and gene expression in ectocervical mucosa biopsies in female sex workers (FSWs; n=50), as compared with control women (CG; n=32). FSWs had low-to-absent HIV-1-specific immune responses with significantly lower CD38 expression on circulating CD4(+) or CD8(+) T-cells (both: P<0.001) together with lower cervical gene expression of genes associated with leukocyte homing and chemotaxis. FSWs also had increased levels of interferon-É› (IFNÉ›) gene and protein expression in the cervical epithelium together with reduced expression of genes associated with HIV-1 integration and replication. A correlative relationship between semen exposure and elevated type-1 IFN expression in FSWs was also established. Overall, our data suggest that long-term condomless sex work can result in multiple changes within the cervico-vaginal compartment that would contribute to sustaining a lower susceptibility for HIV-1 infection in the absence of HIV-specific responses.Mucosal Immunology advance online publication, 11 November 2015; doi:10.1038/mi.2015.116.
Dispatch from the non-HITECH-incented Health IT world: electronic medication history adoption and utilization. - Journal of the American Medical Informatics Association : JAMIA
To document national trends of electronic medication history use in the ambulatory setting and describe the characteristics and predicting factors of providers who regularly use medication history transaction capabilities through their e-prescribing systems.The study used provider-initiated medication history data requests, electronically sent over an e-prescribing network from all 50 states and the District of Columbia. Data from 138,000 prescribers were evaluated using multivariate analyses from 2007 to 2013.Medication history use showed significant growth, increasing from 8 to 850 million history requests during the study period. Prescribers on the network for <5 years had a lower likelihood of requests than those on the network for 5 or more years. Although descriptive analyses showed that prescribers in rural areas were alongside e-prescribing, and requesting medication histories more often than those in large and small cities, these findings were not significant in multivariate analyses. Providers in orthopedic surgery and internal medicine had a higher likelihood of more requests than family practice prescribers, with 12% and 7% higher likelihood, respectively.Early adopters of e-prescribing have remained medication history users and have continually increased their volume of requests for medication histories.Despite the fact that the use of medication histories through e-prescribing networks in the ambulatory care setting has not been encouraged through federal incentive programs, there has been substantial growth in the use of medication histories offered through e-prescribing networks.© The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email:
Dabigatran etexilate and reduction in serum apolipoprotein B. - Heart (British Cardiac Society)
Carboxylesterases, which convert dabigatran etexilate to its active form, dabigatran, have also been shown to influence lipoprotein metabolism, although any pleotropic effects of the drug based on this possible mechanism has not been evaluated. We examined the effects of dabigatran etexilate on serum lipoprotein markers in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) study.2513 participants from the RE-LY randomised control trial with baseline and 3-month apolipoprotein B (ApoB) and apolipoprotein A1 (ApoA1) measurements were included. We prospectively compared the effects of dabigatran 110 mg twice daily, dabigatran 150 mg twice daily and warfarin on changes in ApoB and ApoA1 concentrations using a mixed model analysis.From baseline to 3 months, a significant reduction in ApoB concentration was observed with low-dose dabigatran (-0.057 (95% CI -0.069 to -0.044) g/L, p<0.001) and high-dose dabigatran (-0.065 (95% CI -0.078 to -0.053) g/L, p<0.001) but not warfarin (-0.006 g/L (95% CI -0.018 to 0.007) g/L, p=0.40). Compared with warfarin, ApoB reduction was significantly greater with both doses of dabigatran (p<0.001 for both groups). Reductions in ApoA1 concentrations did not statistically differ with either dose of dabigatran when compared with warfarin.Dabigatran is associated with a significant (∼7%) reduction in ApoB concentration, suggesting a novel effect of this drug on lipoprotein metabolism. Further studies are needed to determine the mechanism of this observed effect, and its impact on clinical outcomes.Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to
Profile of Institutional Ethics Committees in Dental Teaching Institutions in Kerala, India. - Accountability in research
To assess the existence, structure and functioning of Institutional Ethics Committees (IECs) in dental teaching institutions in Kerala.A cross-sectional questionnaire based survey was conducted by personally approaching Heads of Institutions/Ethics committee in-charges of all dental colleges (23 nos.) in Kerala. The validated questionnaire consisted of two parts. First part pertained to details of institutions and second part assessed structure and functioning of IEC. The data obtained was tabulated and analyzed using descriptive statistics.Of the participated 17 colleges, 13 colleges had a functioning IEC. Only 4 of these IEC's were accredited to a central agency. Only one among the 12 colleges completely adhered to recommended structure. Regarding functioning of IEC, 69% of the IECs neither had a separate application form for ethical review of proposals nor a proforma for its evaluation. On an average, more than 10 proposals were reviewed in a single EC meeting in 54% of the colleges. Nearly 40% of the IECs had no representation of a lay person.The absence of IEC in four colleges and non-accreditation to a central agency was a matter of concern. Enforced accreditation is the need of the hour to ensure ethical protection to human participants.
Isosorbide Mononitrate in Heart Failure with Preserved Ejection Fraction. - The New England journal of medicine
Background Nitrates are commonly prescribed to enhance activity tolerance in patients with heart failure and a preserved ejection fraction. We compared the effect of isosorbide mononitrate or placebo on daily activity in such patients. Methods In this multicenter, double-blind, crossover study, 110 patients with heart failure and a preserved ejection fraction were randomly assigned to a 6-week dose-escalation regimen of isosorbide mononitrate (from 30 mg to 60 mg to 120 mg once daily) or placebo, with subsequent crossover to the other group for 6 weeks. The primary end point was the daily activity level, quantified as the average daily accelerometer units during the 120-mg phase, as assessed by patient-worn accelerometers. Secondary end points included hours of activity per day during the 120-mg phase, daily accelerometer units during all three dose regimens, quality-of-life scores, 6-minute walk distance, and levels of N-terminal pro-brain natriuretic peptide (NT-proBNP). Results In the group receiving the 120-mg dose of isosorbide mononitrate, as compared with the placebo group, there was a nonsignificant trend toward lower daily activity (-381 accelerometer units; 95% confidence interval [CI], -780 to 17; P=0.06) and a significant decrease in hours of activity per day (-0.30 hours; 95% CI, -0.55 to -0.05; P=0.02). During all dose regimens, activity in the isosorbide mononitrate group was lower than that in the placebo group (-439 accelerometer units; 95% CI, -792 to -86; P=0.02). Activity levels decreased progressively and significantly with increased doses of isosorbide mononitrate (but not placebo). There were no significant between-group differences in the 6-minute walk distance, quality-of-life scores, or NT-proBNP levels. Conclusions Patients with heart failure and a preserved ejection fraction who received isosorbide mononitrate were less active and did not have better quality of life or submaximal exercise capacity than did patients who received placebo. (Funded by the National Heart, Lung, and Blood Institute; number, NCT02053493 .).
Choline Kinase Beta-Related Muscular Dystrophy, Appearance of Muscle Involvement on Magnetic Resonance Imaging. - Pediatric neurology
Clinical presentation with motor delay, proximal weakness, and learning difficulties will raise the possibility of a dystrophinopathy, dystroglycanopathy, or myotonic dystrophy. This differential should also include the more recently described choline kinase beta-related muscular dystrophy. This condition is typically characterized by large and abnormally distributed mitochondria on muscle biopsy, which can distinguish this condition from the other muscle conditions in the differential.We present a case of a boy with choline kinase beta mutations with relatively mild clinical presentation, including proximal weakness, learning difficulties and raised creatine kinase. Investigations included muscle magnetic resonance imaging (MRI) with T1 axial sequences through thigh and calves, and needle muscle biopsy of the left vastus lateralis muscle.MRI showed involvement mainly of the quadriceps femoris, sartorius, and adductor magnus, with selective sparing of the gracilis, hamstrings, and adductor longus and brevis. Muscle biopsy revealed chronic dystrophic features. Oxidative stains demonstrated enlarged mitochondria accentuated peripherally or present diffusely in a few fibres giving a coarsely stippled appearance. A homozygous C.722A>G (p.Asn241Ser) mutation was detected in exon 6 of the CHKB gene.This selective pattern of skeletal muscle involvement might be helpful for identifying other patients with this condition, even in the absence of diagnostic muscle pathology.Copyright © 2015 Elsevier Inc. All rights reserved.
Sex Differences in Self-Reported Hip Function Up to 2 Years After Arthroscopic Surgery for Femoroacetabular Impingement. - The American journal of sports medicine
Femoroacetabular impingement (FAI) is a significant cause of disability in young adults. Hip arthroscopic surgery restores bony congruence and improves function in the majority of patients, but recent evidence indicates that women may experience worse pre- and postoperative function than men.The purpose of this study was to identify whether self-reported hip function differed between men and women with symptomatic FAI. The hypothesis was that mean self-reported hip function scores would improve after arthroscopic surgery but that women would report poorer function than men both before and up to 2 years after arthroscopic surgery.Cohort study; Level of evidence, 2.A total of 229 patients (68.4% women; mean [±SD] age, 31.6 ± 10.8 years; mean [±SD] body mass index, 26.8 ± 11.9 kg/m(2)) underwent hip arthroscopic surgery for unilateral symptomatic FAI. All eligible and consenting patients with radiologically and clinically confirmed FAI completed the International Hip Outcome Tool (iHOT-33) and the Hip Outcome Score activities of daily living subscale (HOS-ADL) before hip arthroscopic surgery and at 3, 6, 12, and 24 months after arthroscopic surgery. A linear mixed model for repeated measures was used to test for differences in self-reported hip function between men and women over the study period (P ≤ .05).There were no significant time × sex interactions for either the HOS-ADL (P = .12) or iHOT-33 (P = .64), but both measures showed significant improvements between the preoperative time point and each of the 4 follow-up points (P < .0001); however, self-reported hip function did not improve between 6 and 24 months after arthroscopic surgery (P ≥ .11). Post hoc independent t tests indicated that women reported poorer hip function than did men before surgery (P ≤ .003) both on the HOS-ADL (mean ± standard error of the mean [SEM], 67.4 ± 1.9 [men] vs 60.5 ± 1.3 [women]) and iHOT-33 (mean ± SEM, 38.0 ± 1.9 [men] vs 30.9 ± 1.3 [women]); scores were not different between sexes at any other time point.These findings indicate improvements in self-reported hip function in patients with FAI, regardless of sex, until 6 months after hip arthroscopic surgery. Although women reported poorer preoperative function than did men, the differences were not significant 2 years after surgery.© 2015 The Author(s).
A randomized, double-blind, placebo-controlled trial to evaluate the safety and effectiveness of intracoronary application of a novel bioabsorbable cardiac matrix for the prevention of ventricular remodeling after large ST-segment elevation myocardial inf - American heart journal
Postinfarction left ventricular (LV) remodeling can result in chronic heart failure and functional impairment. Although pharmacological strategies for established heart failure can be beneficial, preventing remodeling remains a challenge. Injectable bioabsorbable alginate or "bioabsorbable cardiac matrix" (BCM), composed of an aqueous mixture of sodium alginate and calcium gluconate, is a sterile colorless liquid that is a polysaccharide polymer produced from brown seaweed. When exposed to excess ionized calcium present in infarcted myocardium, BCM assembles to form a flexible gel, structurally resembling extracellular matrix, which provides temporary structural support to the infarct zone through and beyond the time needed for mature fibrotic tissue to develop. The PRESERVATION I trial is an early phase randomized, double-blind, placebo-controlled trial comparing intracoronary application of 4 mL of BCM with saline control in patients who develop large infarctions after successful reperfusion of large ST-segment elevation myocardial infarction (MI). Subjects will be randomized 2:1 to either BCM or saline control and will have the study device deployed through an intracoronary microcatheter in the infarct-related artery 2 to 5 days after index ST-segment elevation MI treated with successful primary or rescue percutaneous coronary intervention. The primary effectiveness end point is the absolute change in LV diastolic volume index as measured by 3-dimensional echocardiography from baseline to 6 months after BCM deployment. Secondary effectiveness end points include clinical outcomes, patient-reported quality of life, additional echocardiographic measures, and functional status measures. In summary, the PRESERVATION I trial is a randomized double-blind trial evaluating the effectiveness and safety of the novel device BCM in preventing LV remodeling patients who have large MIs despite undergoing successful primary or rescue percutaneous coronary intervention.Copyright © 2015 Elsevier Inc. All rights reserved.
Traumatic brain injury advancements. - Current opinion in critical care
Traumatic brain injury (TBI) remains the leading cause of morbidity and mortality in the United States. Over the last decade, several advancements have been made in the field of TBI all aimed at improving outcomes.Advancements in the management of TBI have been made possible through improved understanding of basic pathophysiology associated with this condition. The aim of this review is to briefly highlight the underlying pathophysiology of TBI and the most recent advancements and novel strategies being used in its treatment. We also briefly discuss coagulopathy of TBI, clinical management of TBI and how it has evolved recently.The mortality associated with TBI continues to remain high and several novel strategies have emerged as potential candidates for the treatment of secondary brain injury. The clinical management of TBI and associated coagulopathy has evolved allowing for a more tailored approach toward its management.

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