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At least 109 records · Page 6Linked to original sources

Latin American consensus on the medical oncologic management of early-stage HR+/HER2- breast cancer: Addressing regional disparities in Spanish-speaking countries.

PURPOSE: Substantial disparities persist in managing early-stage hormone receptor-positive, HER2-negative (HR+/HER2-) breast cancer across Spanish-speaking Latin America, including limited access to genomic testing, systemic therapies, and fertility preservation. The Latin American Breast Cancer Association (LABCA) convened an expert panel to produce the first consensus tailored to Spanish-speaking countries. METHODS: A literature review (Embase, PubMed, Scopus, ClinicalKey, LILACS; 2014-2025), informed by ESMO/ASCO/NCCN/SEOM guidelines and registered in PROSPERO (CRD42024565706), supported statement development. A steering committee of three experts of Spanish nationality supervised the process. Twenty-one specialists from 11 countries participated in a modified Delphi process; 31 items were voted in Round 1 and 25 statements were retained within scope. Consensus was pre-defined as ≥80% agreement (or median 7-9), with a mean/outlier rule reported alongside. RESULTS: Applying the ≥80% rule, 22 of 25 statements (88%) reached full consensus; three (1.3, 2.4, 3.3; 75-76%) were near-consensus and retained with caveats. Recommendations integrated clinicopathologic and molecular factors to guide risk stratification; genomic assays were reserved for selected scenarios and discouraged in very low-risk tumors or ≥4 positive lymph nodes. Consensus also covered ovarian suppression plus endocrine therapy, fertility preservation, sexual-health and genetic evaluation, and adjuvant CDK4/6 and PARP inhibitors when accessible. Marked heterogeneity in access was documented by country and sector. CONCLUSION: This consensus provides the first region-specific, evidence-based, resource-adapted recommendations for early-stage HR+/HER2- breast cancer in Spanish-speaking Latin America, aiming to reduce disparities and strengthen equitable oncology care.

Humans

Tuberculosis and HIV infection in sub-Saharan Africa.

OBJECTIVES: To review the epidemiologic, clinical, and pathological characteristics and the public health implications of human immunodeficiency virus (HIV)-associated tuberculosis in sub-Saharan Africa. DATA SOURCES: Published medical literature (English and French) and proceedings of international and African conferences on the acquired immunodeficiency syndrome (AIDS). STUDY SELECTION: Selection by the authors of articles most pertinent to HIV infection and tuberculosis in Africa and internationally. DATA EXTRACTION: Direct reporting of quantitative data (eg, HIV seroprevalence levels) and of qualitative descriptions and conclusions from selected literature. DATA SYNTHESIS: High rates (20% to 67%) of HIV infection in patients with tuberculosis have been reported from East, West, Central, and Southern Africa. An increase in tuberculosis cases has been reported at the same time as the emergence of AIDS in several countries. Autopsies in Abidjan, Ivory Coast (Côte d'Ivoire), have shown tuberculosis as the most frequent opportunistic infection in patients dying of AIDS. Clinical differences in patients with tuberculosis who were HIV-positive and HIV-negative are reviewed, the most important being a greatly increased mortality rate in HIV-associated disease. Access to HIV testing is required for firm diagnosis, for clinical care and counseling, and for public health surveillance. CONCLUSIONS: The epidemiology of tuberculosis has been profoundly influenced by the epidemic of HIV infection in sub-Saharan Africa. Greatly increased human and material resources are required for this neglected problem in international health.

Acquired Immunodeficiency Syndrome

Legal abortion in England and Wales.

Ninety-eight per cent of abortions on British women resident in England or Wales are performed for social reasons. The Abortion Act (1967) insists on the opinion of two doctors but is broadly phrased and, by allowing that abortion can protect mental health, permits abortion when social factors are causing or likely to cause significant stress. The abortion rate has been stable at 11-12 per 1000 women aged 15-44 since 1973, suggesting that factors causing unplanned pregnancy are remaining constant for women in the fertile years and that, overall, the available facilities are adequate. However, only 49% of women obtain a free abortion in the National Health Service (NHS) and there are wide regional variations. Serious delays in the NHS are associated with inadequate access to pregnancy tests, attitudes of medical staff to abortion, and gynaecological units that are fully occupied with other problems. Women can choose to pay for abortions in services run either by charities or by commercial organizations. These services are used electively by a minority of women but most would prefer an NHS abortion if it was easily available. Women who seek help outside the NHS receive prompt and efficient management.

Abortion, Legal

Interaction between parallel transport systems examined with tryptophan and related amino acids.

Most of the neutral amino acids are transported across the plasma membrane by two or more parallel transport systems. In this study, we have limited transport interactions to System A and L by studying amino acids not transported by System ASC. Results are presented to emphasize that such amino acids as leucine, phenylalanine and tryptophan do enter the Ehrlich cell to substantial degrees by System A. We show how the phenomenon of competitive stimulation presents a strong argument that these systems operate between the same two compartments, extracellular and cellular. To discover what is needed to bring two amino acids into the transport relation shown by tryptophan and methionine, we arbitrarily set up two classes of amino acids: (1) those whose steady-state gradients will be increased when System L is deleted; (2) those whose gradients will instead be decreased. On blockading System L with 2-aminorbornane-2-carboxylic acid applied in symmetry to the two sides of the plasma membrane, we show as predicted that the gradient maintained for methionine is strongly increased, that for trypotphan decreased. The initial rate of uptake of all the amino acids mentioned is highly sensitive to the nature of the cellular amino acid pool. A high influx by exchange, relative to net influx, appears to characterize the amino acids that respond to competitive stimulation. Albumin-bound tryptophan appears not directly accessible to the tested carriers.

Animals

Drinking saccharin increases food intake and preference--I. Comparison with other drinks.

To examine the orosensory and postingestive effects of saccharin solution on food intake and food preference, freely feeding rats were given flavored food to eat and a solution to drink for 2 h on eight to ten occasions. Relative to trials with a different flavored food and only water to drink, food intake was increased by drinking 0.2% saccharin or 0.45% NaCl, unaffected by drinking 1% almond extract, and decreased by drinking 10% glucose. Food preference, which was assessed in a choice test with simultaneous access to the two flavored foods, was increased by drinking 0.2% saccharin or 10% glucose and unaffected by drinking 1% almond extract or 0.45% NaCl. These results are consistent with the possibility that a combination of the oral and hydrational properties of saccharin solution increase food intake. Saccharin's sweet taste may be responsible for its effects on food preference.

Animals

Penetration of IgGs into the neuraxis of the neonatal rat.

The permeability of the mammalian blood-brain barrier to macromolecules during prenatal and postnatal development is a controversial issue. We tested the possible access of xenogeneic antibodies to the neuraxis by examining neural tissue of neonatal rats 48 h after intraperitoneal injection of rabbit IgGs, using a modification of the peroxidase-antiperoxidase (PAP) technique. The results of the present study indicate diffuse immunoreactivity for rabbit IgGs in the parenchyma in all regions of the neuraxis in neonatal rats. This work suggests that immunoglobulins, both maternal and isogeneic, may affect the nervous system during prenatal and postnatal development.

Animals

Correlates of performance on the Gollin and Mooney tests of visual closure.

One hundred and twenty-seven undergraduate students variously performed a computerized version of the Gollin (1960) Incomplete Figures Test, the Mooney (1957) Test of Incomplete Face Perception, the Poppelreuter (1917) Overlapping Figures Test, and a visual search task. Performance of male subjects was superior to that of female subjects on the Mooney test but inferior on the visual search task. Correlation and regression analyses showed that the only significant predictor of Gollin test scores was latency to identify all items in the Overlapping Figures Test. There was no relationship between performances on the Gollin and Mooney tests or between Gollin or Mooney test performance and visual search latency. The Gollin and Mooney tests appear to access different perceptual processes, none of which is dependent on the efficiency of visual search.

Adolescent

A Randomized Clinical Trial to Compare Moxifloxacin Versus Azithromycin for the Treatment of Mycoplasma genitalium: The FARTHEST Study.

BACKGROUND: Mycoplasma genitalium (MG) is increasingly characterized by high rates of macrolide and fluoroquinolone resistance. International guidelines recommend resistance-guided therapy; however, access to genotypic testing is limited, and randomized trial evidence is lacking. We assessed the efficacy of moxifloxacin and azithromycin without resistance assays. METHODS: This monocentric, open-label, superiority, randomized controlled trial enrolled adults with MG infection detected by multiplex PCR, randomized 1:1 to receive moxifloxacin 400 mg daily for 10 days or azithromycin 500 mg daily for 6 days. A test of cure was performed ≥28 days after treatment completion. The primary endpoint was microbiological cure in the intention-to-treat (ITT) and per-protocol (PP) populations. Subgroup analyses assessed symptomatic versus asymptomatic infections, doxycycline exposure, re-treatment, and sexual behavior. RESULTS: Among 358 randomized participants, 87.0% of those treated with moxifloxacin and 61.2% of those treated with azithromycin achieved microbiological cure in the ITT analysis (absolute risk difference 25.8%, 95% CI 16.5, 35.2). The superiority of moxifloxacin was confirmed in the ITT and PP populations. Moxifloxacin remained superior across most subgroups, whereas azithromycin showed comparable efficacy only among heterosexual individuals. Doxycycline coadministration did not improve outcomes. Both regimens were well tolerated, with only one case of discontinuation. CONCLUSIONS: Moxifloxacin demonstrated superior efficacy compared to azithromycin for treating MG infection in the absence of resistance testing. These randomized data support the use of moxifloxacin as a first-line option when resistance assays are unavailable and may inform treatment strategies.

Humans

Sitosterolemia: evolving strategies for earlier diagnosis.

PURPOSE OF REVIEW: Sitosterolemia is a rare autosomal recessive lipid disorder caused by biallelic pathogenic variants in ABCG5 or ABCG8 , resulting in excessive intestinal absorption and impaired biliary excretion of plant sterols. Although historically considered exceptionally rare, recent genetic studies suggest the disorder is substantially underdiagnosed, with marked phenotypic heterogeneity ranging from xanthomas and premature atherosclerosis to hematologic abnormalities, and frequently mimics familial hypercholesterolemia. This review summarizes recent advances in the clinical, biological, and genetic diagnosis of sitosterolemia, with a focus on strategies that may facilitate earlier detection. RECENT FINDINGS: Phytosterol quantification, particularly sitosterol, campesterol, and stigmasterol, remains indispensable for accurate diagnosis. Hematologic abnormalities, including hemolytic anemia, stomatocytosis, and macrothrombocytopenia, are increasingly recognized as valuable diagnostic clues complementing the biochemical approach. Expanded variant catalogs for ABCG5/ABCG8 and genome-wide association studies have revealed potentially polygenic contributions to phytosterol metabolism extending beyond these two genes. However, no specific guidelines have yet been established for cascade screening. SUMMARY: Earlier diagnosis requires integration of clinical, biochemical, hematologic, and genetic data. Plasma phytosterol measurement remains the diagnostic cornerstone. Improved disease awareness, broader access to sterol testing, and expanded genetic screening may reduce diagnostic delays and enable timely management, including ezetimibe and dietary phytosterol restriction.

Humans

A follow-up study of 68 patients with anti-mitochondrial antibodies (AMA).

During the period 1976-83, anti-mitochondrial antibodies (AMA) were detected in 68 patients out of about 48 000 sera (0.14%) analyzed for a repertoire of autoantibodies at the Department of Immunology, University Hospital of Tromsø. Fifty-five of these patients were women, and only 10 had unequivocal primary biliary cirrhosis (PBC). At follow-up in 1984, 48 out of these 68 patients were accessible for complementary testing. The AMA test became negative in 17 of these 48 patients during the observation period. Eleven of these 17 had originally a titer of 50. Seven of the 31 patients with persistent AMA were without detectable liver pathology. One patient had antibodies against smooth muscle, one against cell nucleus, whereas 35 had an increased serum IgM level. In conclusion, most patients with AMA do not have obvious PBC, a low AMA titer is likely to be transient, and there is a strong association between AMA and an increased serum IgM level.

Adult

Genetic diversity and molecular mechanisms in hypertrophic cardiomyopathy: toward personalized therapy.

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac muscle disorder, yet contemporary genomic and mechanistic research still lacks a cohesive model explaining how diverse genetic architectures give rise to heterogeneous phenotypes. This review synthesizes advances across sarcomeric and nonsarcomeric mutations, including intermediate-effect variants, polygenic modifiers, and ancestry-dependent sources of variant misclassification to elucidate how these factors govern disease penetrance and clinical expression. It critically evaluates how genetic diversity intersects with key molecular pathways, including sarcomeric hypercontractility, calcium dysregulation, mitochondrial energy deficiency, and transforming growth factor-β (TGF-β) and protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling, to drive hypertrophic and fibrotic remodeling. Emerging mechanism-based therapies, such as myosin inhibition, allele-specific silencing, clustered regularly interspaced short palindromic repeats (CRISPR)-based correction, and metabolic modulation, are examined with respect to their capacity to modify upstream molecular drivers rather than downstream hemodynamic consequences. Persistent challenges, including variants of uncertain significance classification, ancestry-biased databases, inequitable access to genetic testing, and unresolved safety concerns for gene-based therapies, are critically assessed as major barriers to precision-medicine integration. By linking genetic architecture, molecular pathogenesis, and targeted interventions, this review advances a contemporary, mechanistically grounded framework that informs both individualized management and future research directions. Future research should prioritize pathway-specific therapeutics, functional and mechanistic validation of emerging variants, deeper physiologic phenotyping to refine disease modeling, and accelerate translation throughout the continuum of HCM pathophysiology.

Humans

Systemic treatment of advanced pancreatic cancer: A Comprehensive Review.

IMPORTANCE: Pancreatic adenocarcinoma (PDAC) is an uncommon but potentially catastrophic diagnosis with historically poor prognosis. It is the tenth most prevalent cancer in the US & UK. Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies worldwide, with a five-year survival rate of approximately 10%. Despite increasing understanding of its molecular biology, systemic treatment options for advanced disease remain limited, and survival outcomes have improved only modestly over the past decade. OBSERVATIONS: This narrative review traces the evolution of systemic therapy for advanced PDAC from gemcitabine monotherapy through the landmark FOLFIRINOX (PRODIGE trial) and gemcitabine/nab-paclitaxel (MPACT trial) combination regimens, which remain the standard of care. Second-line options including liposomal irinotecan plus 5-FU/LV (NAPOLI-1) and maintenance olaparib for germline BRCA1/2-mutated disease (POLO) are also reviewed. Emerging data on sequential treatment strategies (SEQUENCE trial), biomarker-driven treatment selection (PRIMUS-001, PASS-01), and precision medicine approaches targeting actionable molecular subgroups, including dMMR/MSI-H, NTRK fusions, and homologous recombination deficiency are discussed. Real-world evidence comparing FOLFIRINOX and gemcitabine/nab-paclitaxel is critically appraised, including the challenges of patient selection, tolerance, and applicability outside clinical trial settings. CONCLUSION AND RELEVANCE: Despite incremental progress, the treatment landscape of advanced PDAC remains challenging. Molecular stratification and biomarker-driven precision oncology represent the most promising path forward. This review serves as a clinical reference for physicians managing advanced pancreatic cancer, highlighting current evidence, evidence limitations, and future research priorities including prospective biomarker-driven trials and improved access to genomic testing.

Biomarkers

Cancer control in Louisiana: assessment of needs and development of a plan.

A cancer control plan for Louisiana has been developed by the Office of Public Health with funding from the National Cancer Institute. Priorities in the plan are the prevention of cancer through tobacco control and improved nutrition and the early detection of cancer through increased access to screening tests. Findings of the task forces and pilot cancer control interventions planned for Louisiana are described.

Health Promotion

[Pharmacokinetic studies of "Pharmachem" tylosin with healthy and infectious epididymitis-affected rams].

The retention in blood and the excretion with semen were followed up of tylosin-base, product of the State Economic Corporation "Pharmachim" (People's Republic of Bulgaria). It was found that at muscular application (12 mg/kg) the preparation is resorbed at the site of injection and is retained at a therapeutic level concentration in the blood of rams in the course of 24 to 26 hours. Tylosin gains access to the testes and is excreted with the semen at the same rate as in infectious epididymitis-intact rams. No correlation has been observed between the blood level of tylosin and the content of tylosin in the spermal plasma. The single treatment of rams with tylosin at the dosing cited above is not able to arrest the excretion of Brucella organisms with the semen, and does not improve its morphologic composition.

Animals

Menstrual cycle influences on operant behavior of female rhesus monkeys.

Nine female rhesus monkeys were paired with males throughout 63 menstrual cycles. The females' motivation to approach males was studied with an operant conditioning paradigm that required the female to press a lever 250 times to gain access to the male. Sexual behavior was scored during standard 60-min tests that followed the attainment of access (17 pairs, 1,440 tests). In the overall data, mean times to access were shortest at mid-cycle and longest just before and after the onset of menstruation, and a model-fitting method showed that 45% of cycles from individual pairs were significantly correlated with a V-shaped model of the overall pattern. Male sexual activity was highest at mid-cycle and lowest in the last quarter of the cycle, but the changes in access times could not be attributed entirely to the rewarding effects of the ejaculations. In the combined data from five females (9 pairs, 33 cycles), high estradiol levels and low progesterone levels were statistically associated with short access times and short ejaculation times. The overall effect was for operant performance and sexual activity to be synchronized and maximized in the periovulatory period of the menstrual cycle.

Animals

Genetic testing practices across European epilepsy centers: An ERN EpiCARE survey.

OBJECTIVE: Genetic testing plays an increasing role in the diagnostic pathway for rare and complex epilepsies. However, significant heterogeneity persists in access, implementation, and interpretation across Europe. This study aimed to assess genetic testing practices, accessibility, and challenges across expert epilepsy centers within the European Reference Network for Rare and Complex Epilepsies (ERN EpiCARE) and to identify key challenges and areas for harmonization. METHODS: A cross-sectional survey was developed by the ERN EpiCARE Clinical Genetics Working Group and distributed to 50 EpiCARE member centers across 27 European countries. The questionnaire collected quantitative and qualitative information on available genetic testing modalities, turnaround times, use of rapid testing, multidisciplinary team (MDT) organization, genetic counseling practices, and perceived challenges. Survey findings were complemented by a structured discussion held during the ERN EpiCARE General Assembly. RESULTS: Responses were received from 46 centers (51 responses). Most centers reported access to genetic testing, predominantly through in-house facilities. Whole-exome sequencing was available in 85% of centers, and gene panels were available in 78%. Whole-genome sequencing was available in 59% of centers, frequently restricted to research or performed externally. Turnaround times for standard genetic testing were most commonly between 1 and 6 months. Genetic testing strategies varied by epilepsy subtype, with gene panels most frequently used as first-tier testing, and exome sequencing preferentially applied in developmental and epileptic encephalopathies. Considerable heterogeneity was observed in MDT organization, access to genetic counseling, reimbursement, data-sharing and registry infrastructures. SIGNIFICANCE: Although genetic testing is widely available across ERN EpiCARE centers, substantial disparities persist in its organization, accessibility, and implementation. Addressing these gaps through strengthened multidisciplinary collaboration, harmonized diagnostic strategies, and enhanced European-level coordination will be essential to ensure equitable access to high-quality genetic care for individuals with epilepsy. PLAIN LANGUAGE SUMMARY: Genetic testing is increasingly integrated in the diagnostic pathway for rare and complex epilepsies and treatment decisions. An ERN EpiCARE survey assessed how genetic testing is implemented across specialist epilepsy centers in Europe and identified persistent organizational, financial, and clinical barriers. Although most centers had access to advanced genomic testing, important differences were identified in access, reimbursement, turnaround times, and multidisciplinary expertise. European collaboration and harmonized practices are needed to support equitable access to high-quality genetic care for people living with epilepsy.

European reference networks

Hereditary cancer: Germline testing practices across ERN GENTURIS member countries.

Germline genetic testing practices for hereditary cancer vary across the European Reference Network on Genetic Tumour Risk Syndromes (ERN GENTURIS) member countries. We surveyed experts in genetic testing from 20 EU member countries and Norway to assess multi-gene panel usage, availability of genome-wide sequencing, first-tier testing approaches, implementation of polygenic risk scores, and the roles of non-genetic healthcare professionals. National experts and members of the ERN GENTURIS completed a structured questionnaire covering founder germline pathogenic variants (gPV) testing, panel testing for common genetic tumour risk syndromes, use of whole-exome sequencing (WES) and whole-genome sequencing, polygenic risk score implementation, use of formalin-fixed paraffin-embedded tumour samples, laboratory accreditation, and the clinical roles of physicians, genetic counselors and nurses. Significant inter-country heterogeneity was observed. Most countries rely on next-generation sequencing (NGS) multi-gene panels. Founder gPV testing is first-line in a few high-prevalence populations (e.g., BRCA1/2 founders). All 21 countries offer NGS panel tests for hereditary breast and ovarian cancer, and ≥19 countries do so for colorectal and prostate cancers. However, NGS panel size and gene composition exhibit substantial variability. WES is available in 12 countries on a routine basis. Most countries implemented genetic testing on stored tumour tissue from deceased patients. In all countries, clinical geneticists can order germline genetic tests, and in 9 countries, any physician can do so. These findings show differences in accessibility to germline genetic testing of hereditary cancer in Europe. We propose EU-wide guidance via pathways, standards of care, and sharing of best practices to further optimize access to hereditary cancer genetic molecular diagnostics.

Humans

[Surgical approaches to the liver and spleen].

A three-edge arbalest access to subdiaphragmatic organs is suggested. The access in its total or partial extent was tested in 393 operations. This access is considered to be more advantageous as compared with the analogous known ones.

Evaluation Studies as Topic