Tissue Inhibitor of Metalloproteinase-1 Concentrations are Attenuated in Peritoneal Fluid and Sera of Women with Endometriosis and Restored in Sera by Gonadotropin-Releasing Hormone Agonist Therapy

Objective: To establish tissue inhibitor of metalloproteinase-1 (TIMP-1) concentrations in peritoneal fluid (PF) and sera of women with endometriosis and compare them to disease-free controls.

Design: Prospective randomized study.

Setting: Academic medical center.

Patient(s): Women with laparoscopically documented endometriosis and disease-free women of reproductive age.

Intervention(s): Peritoneal fluid and sera were collected, and some women received gonadotropin-releasing hormone agonist (GnRH-a) therapy for endometriosis.

Main Outcome Measure(s): Peritoneal fluid and sera TIMP-1 concentrations were measured with a specific RIA.

Result(s): The TIMP-1 concentrations were significantly lower in PF and sera of women with endometriosis compared with disease-free women. The GnRH-a therapy restored serum TIMP-1 concentrations.

Conclusion(s): Aberrant expression and localization of TIMP-1 may derange the proteolytic milieu of the peritoneal cavity and contribute to the etiology and underlying physiologic sequelae associated with endometriosis. Measurement of TIMP-1 in serum may aid in diagnosing endometriosis and assist with monitoring treatment efficacy in women with this disease.     

Prevalence of potentially severe drug-drug interactions in ambulatory patients with dyslipidaemia receiving HMG-CoA reductase inhibitor therapy.

BACKGROUND: Drug-drug interactions (DDIs) are a well known risk factor for adverse drug reactions. HMG-CoA reductase inhibitors ('statins') are a cornerstone in the treatment of dyslipidaemia and patients with dyslipidaemia are concomitantly treated with a variety of additional drugs. Since DDIs are associated with adverse reactions, we performed a cross-sectional study to assess the prevalence of potentially critical drug-drug and drug-statin interactions in an outpatient adult population with dyslipidaemia. METHODS: Data from patients with dyslipidaemia treated with a statin were collected from 242 practitioners from different parts of Switzerland. The medication list was screened for potentially harmful DDIs with statins or other drugs using an interactive electronic drug interaction program. RESULTS: We included 2742 ambulatory statin-treated patients (mean age +/- SD 65.1 +/- 11.1 years; 61.6% males) with (mean +/- SD) 3.2 +/- 1.6 diagnoses and 4.9 +/- 2.4 drugs prescribed. Of those, 190 patients (6.9%) had a total of 198 potentially harmful drug-statin interactions. Interacting drugs were fibrates or nicotinic acid (9.5% of patients with drug-statin interactions), cytochrome P450 (CYP) 3A4 inhibitors (70.5%), digoxin (22.6%) or ciclosporin (cyclosporine) [1.6%]. The proportion of patients with a potential drug-statin interaction was 12.1% for simvastatin, 10.0% for atorvastatin, 3.8% for fluvastatin and 0.3% for pravastatin. Additionally, the program identified 393 potentially critical non-statin DDIs in 288 patients. CONCLUSIONS: CYP3A4 inhibitors are the most frequent cause of potential drug interactions with statins. As the risk for developing rhabdomyolysis is increased in patients with drug-statin interactions, clinicians should be aware of the most frequently observed drug-statin interactions and how these interactions can be avoided.     

Immunohistochemical expression of DNA repair proteins in familial breast cancer differentiate BRCA2-associated tumors.

PURPOSE: Morphologic and immunohistochemical studies of familial breast cancers have identified specific characteristics associated with BRCA1 mutation-associated tumors when compared with BRCA2 and non-BRCA1/2 tumors, but have not identified differences between BRCA2 and non-BRCA1/2 tumors. Because BRCA1 and BRCA2 genes participate in the DNA repair pathway, we have performed an immunohistochemical study with markers related to this pathway to establish the profile of the three groups. MATERIALS AND METHODS: We have studied two tissue microarrays that include 103 familial and 104 sporadic breast tumors, with a panel of DNA repair markers including ATM, CHEK2, RAD51, RAD50, XRCC3, and proliferating cell nuclear antigen. RESULTS: We found more frequent expression of CHEK2 in BRCA1 and BRCA2 tumors than in non-BRCA1/2 and sporadic tumors. We found absence of nuclear expression and presence of cytoplasmic expression of RAD51 in BRCA2 tumors that differentiate them from other familial tumors. We validated these results with a new series of patient cases. The final study with 253 familial patient cases (74 BRCA1, 71 BRCA2, 108 non-BRCA1/2), and 288 sporadic patient cases, has allowed us to confirm our preliminary results. Because BRCA2 tumors present a specific immunohistochemical profile for RAD51 and CHEK2 markers that is different from non-BRCA1/2 tumors, we have built a multivariate model with these markers that distinguish both tumors with an estimated probability of at least 76%. CONCLUSION: Our results suggest that BRCA2 tumors demonstrate more cytoplasmic and less nuclear RAD51 staining, and increased CHEK2 staining. This pattern may distinguish BRCA2 from familial non-BRCA1/2 tumors.     

Promoting Informed Decisions About Colorectal Cancer Screening in Older Adults (PRIMED Study): a Physician Cluster Randomized Trial

BackgroundFor adults aged 76–85, guidelines recommend individualizing decision-making about whether to continue colorectal cancer (CRC) testing. These conversations can be challenging as they need to consider a patient’s CRC risk, life expectancy, and preferences.ObjectiveTo promote shared decision-making (SDM) for CRC testing decisions for older adults.DesignTwo-arm, multi-site cluster randomized trial, assigning physicians to Intervention and Comparator arms. Patients were surveyed shortly after the visit to assess outcomes. Analyses were intention-to-treat.Participants and SettingPrimary care physicians affiliated with 5 academic and community hospital networks and their patients aged 76–85 who were due for CRC testing and had a visit during the study period.InterventionsIntervention arm physicians completed a 2-h online course in SDM communication skills and received an electronic reminder of patients eligible for CRC testing shortly before the visit. Comparator arm received reminders only.Main MeasuresThe primary outcome was patient-reported SDM Process score (range 0–4 with higher scores indicating more SDM); secondary outcomes included patient-reported discussion of CRC screening, knowledge, intention, and satisfaction with the visit.Key ResultsSixty-seven physicians (Intervention n=34 and Comparator n=33) enrolled. Patient participants (n=466) were on average 79 years old, 50% with excellent or very good self-rated overall health, and 66% had one or more prior colonoscopies. Patients in the Intervention arm had higher SDM Process scores (adjusted mean difference 0.36 (95%CI (0.08, 0.64), p=0.01) than in the Comparator arm. More patients in the Intervention arm reported discussing CRC screening during the visit (72% vs. 60%, p=0.03) and had higher intention to follow through with their preferred approach (58.0% vs. 47.1, p=0.03). Knowledge scores and visit satisfaction did not differ significantly between arms.ConclusionPhysician training plus reminders were effective in increasing SDM and frequency of CRC testing discussions in an age group where SDM is essential.Trial RegistrationThe trial is registered on clinicaltrials.gov ({"type":"clinical-trial","attrs":{"text":"NCT03959696","term_id":"NCT03959696"}}NCT03959696).Supplementary InformationThe online version contains supplementary material available at 10.1007/s11606-022-07738-4.KEY WORDS: shared decision-making, colorectal cancer screening, patient preferences/patient engagement, online training     

Influence of Documented Lead Poisoning on Environmental Modification Programs in Newark,New Jersey

Data from the Newark, New Jersey Childhood Lead Poisoning Program suggest that the major consequence of the program has been early intervention rather than the amelioration of environmental contamination. During 1975 to 1976, the authors investigated housing for 253 black and Hispanic children with blood levels over 60 Mg/100 ml. Of these, 115 had moved or had given incorrect addresses and were lost to follow-up, 22 were in the same homes but did not make themselves available and in 16 instances, the houses were boarded up or had been destroyed by fire. Of the remaining 100 children, 31% suffered from symptoms potentially related to lead poisoning and 57% of the children were still living in the same dwelling in which the c h id was affected. Only one-fourth of the houses had been properly abated, i. e., the problem of environmental lead had been corrected, and one-fourth of the houses were not investigated at all by health authorities. These data support the concern that lead poisoning will not be effectively combated until the environmental issue is fully addressed.     

Circumcision Status and Time to Sexual Debut Among Youth in Sub-Saharan Africa: Evidence from Six Demographic and Health Surveys

This paper examines the relationship between circumcision status and timing of sexual debut among unmarried youth in Sub-Saharan Africa using Demographic and Health Surveys. Results from survival analysis indicate that the association between circumcision and timing of first sex is place and context specific. Compared to uncircumcised, circumcised men in Rwanda, Uganda and Namibia hasten sexual initiation, whilst circumcised youth in Ethiopia and Mali delayed sex initiation. In Togo however, we found parity in timing to sexual debut. Our multivariate results reveal that, knowledge of HIV/AIDS risk and educational level also feed into the association between circumcision and timing of sex initiation- implying that efforts to prevent new HIV infection through circumcision could benefit from a proper understanding of how diverse set of factors interact in specific contexts to shape youth’s decisions to initiate early sex.     

Carotid webs and ischemic stroke: Experiences in a comprehensive stroke center

Background and purpose

Carotid webs are intraluminal filling defects at the carotid bulb which are considered rare, though possibly underappreciated entities with recent studies demonstrating a likely casual association with ischemic stroke. The purpose of the study is to describe our recent experience with clinical and imaging manifestations of carotid webs.