Mind the gap in kidney care: translating what we know into what we do.

Historically, it takes an average of 17 years to move new treatments from clinical evidence to daily practice. Given the highly effective treatments now available to prevent or delay kidney disease onset and progression, this is far too long. The time is now to narrow the gap between what we know and what we do. Clear guidelines exist for the prevention and management of common risk factors for kidney disease, such as hypertension and diabetes, but only a fraction of people with these conditions worldwide are diagnosed, and even fewer are treated to target. Similarly, the vast majority of people living with kidney disease are unaware of their condition, because in the early stages it is often silent. Even among patients who have been diagnosed, many do not receive appropriate treatment for kidney disease. Considering the serious consequences of kidney disease progression, kidney failure, or death, it is imperative that treatments are initiated early and appropriately. Opportunities to diagnose and treat kidney disease early must be maximized beginning at the primary care level. Many systematic barriers exist, ranging from patient to clinician to health systems to societal factors. To preserve and improve kidney health for everyone everywhere, each of these barriers must be acknowledged so that sustainable solutions are developed and implemented without further delay.

Mind the gap in kidney care: Translating what we know into what we do.

Historically, it takes an average of 17 years to move new treatments from clinical evidence to daily practice. Given the highly effective treatments now available to prevent or delay kidney disease onset and progression, this is far too long. The time is now to narrow the gap between what we know and what we do. Clear guidelines exist for the prevention and management of common risk factors for kidney disease, such as hypertension and diabetes, but only a fraction of people with these conditions worldwide are diagnosed, and even fewer are treated to target. Similarly, the vast majority of people living with kidney disease are unaware of their condition, because in the early stages it is often silent. Even among patients who have been diagnosed, many do not receive appropriate treatment for kidney disease. Considering the serious consequences of kidney disease progression, kidney failure, or death, it is imperative that treatments are initiated early and appropriately. Opportunities to diagnose and treat kidney disease early must be maximized beginning at the primary care level. Many systematic barriers exist, ranging from patient to clinician to health systems to societal factors. To preserve and improve kidney health for everyone everywhere, each of these barriers must be acknowledged so that sustainable solutions are developed and implemented without further delay.

Mind the Gap in Kidney Care: Translating What We Know Into What We do.

Historically, it takes an average of 17 years to move new treatments from clinical evidence to daily practice. Given the highly effective treatments now available to prevent or delay kidney disease onset and progression, this is far too long. The time is now to narrow the gap between what we know and what we do. Clear guidelines exist for the prevention and management of common risk factors for kidney disease, such as hypertension and diabetes, but only a fraction of people with these conditions worldwide are diagnosed, and even fewer are treated to target. Similarly, the vast majority of people living with kidney disease are unaware of their condition, because in the early stages, it is often silent. Even among patients who have been diagnosed, many do not receive appropriate treatment for kidney disease. Considering the serious consequences of kidney disease progression, kidney failure, or death, it is imperative that treatments are initiated early and appropriately. Opportunities to diagnose and treat kidney disease early must be maximized beginning at the primary-care level. Many systematic barriers exist, ranging from patient to clinician to health systems to societal factors. To preserve and improve kidney health for everyone everywhere, each of these barriers must be acknowledged so that sustainable solutions are developed and implemented without further delay.

Mind the gap in kidney care: Translating what we know into what we do.

Historically, it takes an average of 17 years to move new treatments from clinical evidence to daily practice. Given the highly effective treatments now available to prevent or delay kidney disease onset and progression, this is far too long. The time is now to narrow the gap between what we know and what we do. Clear guidelines exist for the prevention and management of common risk factors for kidney disease, such as hypertension and diabetes, but only a fraction of people with these conditions worldwide are diagnosed, and even fewer are treated to target. Similarly, the vast majority of people living with kidney disease are unaware of their condition, because in the early stages it is often silent. Even among patients who have been diagnosed, many do not receive appropriate treatment for kidney disease. Considering the serious consequences of kidney disease progression, kidney failure, or death, it is imperative that treatments are initiated early and appropriately. Opportunities to diagnose and treat kidney disease early must be maximized beginning at the primary care level. Many systematic barriers exist, ranging from patient to clinician to health systems to societal factors. To preserve and improve kidney health for everyone everywhere, each of these barriers must be acknowledged so that sustainable solutions are developed and implemented without further delay.

Mind the Gap in Kidney Care: Translating What We Know Into What We Do.

Historically, it takes an average of 17 years to move new treatments from clinical evidence to daily practice. Given the highly effective treatments now available to prevent or delay kidney disease onset and progression, this is far too long. The time is now to narrow the gap between what we know and what we do. Clear guidelines exist for the prevention and management of common risk factors for kidney disease, such as hypertension and diabetes, but only a fraction of people with these conditions worldwide are diagnosed, and even fewer are treated to target. Similarly, the vast majority of people living with kidney disease are unaware of their condition, because in the early stages it is often silent. Even among patients who have been diagnosed, many do not receive appropriate treatment for kidney disease. Considering the serious consequences of kidney disease progression, kidney failure, or death, it is imperative that treatments are initiated early and appropriately. Opportunities to diagnose and treat kidney disease early must be maximized beginning at the primary care level. Many systematic barriers exist, ranging from patient to clinician to health systems to societal factors. To preserve and improve kidney health for everyone everywhere, each of these barriers must be acknowledged so that sustainable solutions are developed and implemented without further delay. DOI: 10.52547/ijkd.8216.

Mind the gap in kidney care: translating what we know into what we do.

Historically, it takes an average of 17 years to move new treatments from clinical evidence to daily practice. Given the highly effective treatments now available to prevent or delay kidney disease onset and progression, this is far too long. The time is now to narrow the gap between what we know and what we do. Clear guidelines exist for the prevention and management of common risk factors for kidney disease, such as hypertension and diabetes, but only a fraction of people with these conditions worldwide are diagnosed, and even fewer are treated to target. Similarly, the vast majority of people living with kidney disease are unaware of their condition, because in the early stages it is often silent. Even among patients who have been diagnosed, many do not receive appropriate treatment for kidney disease. Considering the serious consequences of kidney disease progression, kidney failure, or death, it is imperative that treatments are initiated early and appropriately. Opportunities to diagnose and treat kidney disease early must be maximized beginning at the primary care level. Many systematic barriers exist, ranging from patient to clinician to health systems to societal factors. To preserve and improve kidney health for everyone everywhere, each of these barriers must be acknowledged so that sustainable solutions are developed and implemented without further delay.

Real-life use of tolvaptan in ADPKD: a retrospective analysis of a large Canadian cohort.

Tolvaptan is the first disease-modifying drug proven to slow eGFR decline in high-risk patients with ADPKD. However, barriers from the patient perspective to its use in real-life settings have not been systemically examined in a large cohort. This was a single-center, retrospective study of 523 existing or new patients with ADPKD followed at the Center for Innovative Management of PKD in Toronto, Ontario, between January 1, 2016 to December 31, 2018. All patients underwent clinical assessment including total kidney volume measurements and Mayo Clinic Imaging Class (MCIC). Those who were deemed to be at high risk were offered tolvaptan with their preference (yes or no) and reasons for their choices recorded. Overall, 315/523 (60%) patients had MCIC 1C-1E; however, only 96 (30%) of them were treated with tolvaptan at their last follow-up. Among these high-risk patients, those not treated versus treated with tolvaptan were more likely to have a higher eGFR (82 ± 26 vs. 61 ± 27 ml/min/1.73 m2), CKD stages 1-2 (79% vs. 41%), and MCIC 1C (63% vs. 31%). The most common reasons provided for not taking tolvaptan were lifestyle preference related to the aquaretic effect (51%), older age ≥ 60 (12%), and pregnancy/family planning (6%). In this real-world experience, at least 60% of patients with ADPKD considered to be at high risk for progression to ESKD by imaging were not treated with tolvaptan; most of them had early stages of CKD with well-preserved eGFR and as such, were prime targets for tolvaptan therapy to slow disease progression. Given that the most common reason for tolvaptan refusal was the concern for intolerability of the aquaretic side-effect, strategies to mitigate this may help to reduce this barrier to tolvaptan therapy.

Exploring Piezo1, Piezo2, and TMEM150C in human brain tissues and their correlation with brain biomechanical characteristics.

Unraveling the intricate relationship between mechanical factors and brain activity is a pivotal endeavor, yet the underlying mechanistic model of signaling pathways in brain mechanotransduction remains enigmatic. To bridge this gap, we introduced an in situ multi-scale platform, through which we delineate comprehensive brain biomechanical traits in white matter (WM), grey-white matter junctions (GW junction), and the pons across human brain tissue from four distinct donors. We investigate the three-dimensional expression patterns of Piezo1, Piezo2, and TMEM150C, while also examining their associated histological features and mechanotransduction signaling networks, particularly focusing on the YAP/ß-catenin axis. Our results showed that the biomechanical characteristics (including stiffness, spring term, and equilibrium stress) associated with Piezo1 vary depending on the specific region. Moving beyond Piezo1, our result demonstrated the significant positive correlations between Piezo2 expression and stiffness in the WM. Meanwhile, the expression of Piezo2 and TMEM150C was shown to be correlated to viscoelastic properties in the pons and WM. Given the heterogeneity of brain tissue, we investigated the three-dimensional expression of Piezo1, Piezo2, and TMEM150C. Our results suggested that three mechanosensitive proteins remained consistent across different vertical planes within the tissue sections. Our findings not only establish Piezo1, Piezo2, and TMEM150C as pivotal mechanosensors that regulate the region-specific mechanotransduction activities but also unveil the paradigm connecting brain mechanical properties and mechanotransduction activities and the variations between individuals.

The benefit of vegetarian diets for reducing blood pressure in Taiwan: a historically prospective cohort study.

OBJECTIVE: Past vegetarians research has often found that they have lower blood pressure (BP). Effects may include their lower BMI and higher intake levels of fruit and vegetables. Besides, the study pursues to extend this evidence in a diverse population containing vegans, lacto-ovo vegetarians and omnivores. DESIGN: The study analyzed data on five hundred vigorous individuals aged 20 years or older from a standard medical screening program and provided validated questionnaire. Criteria were established for vegan, lacto-ovo vegetarian, partial vegetarian and omnivorous dietary patterns. SETTING: Health screening programs were conducted at a standard medical screening program in Taiwan between 2006 and 2017. Dietary data were gathered by self-administered questionnaire. SUBJECTS: Five hundred Taiwanese subjects representing the cohort. RESULTS: Multiple regression analyses confirmed that the vegan vegetarians had lower systolic and diastolic BP (mmHg) than omnivorous Taiwanese (ß = - 6.8, p < 0.05 and ß = - 6.9, p < 0.001). Findings for lacto-ovo vegetarians (ß = - 9.1, p < 0.001 and ß = - 5.8, p < 0.001) were similar. The vegetarians were also less likely to be using antihypertensive medications. Defining hypertension as systolic BP > 139 mmHg or diastolic BP > 89 mmHg or routine of antihypertensive medications, the odds ratio of hypertension compared with omnivores was 0.37 (95% CI = 0.19-0.74), 0.57 (95% CI = 0.36-0.92) and 0.92 (95% CI = 0.50-1.70), respectively, for vegans, lacto-ovo vegetarians and partial vegetarians. Results were reduced after adjustment for BMI. CONCLUSIONS: The study concludes from this relatively large study that vegetarians, especially vegans, with otherwise diverse characteristics but stable diets, do have lower systolic and diastolic BP and less hypertension than omnivores.

BK channels of five different subunit combinations underlie the de novo KCNMA1 G375R channelopathy.

The molecular basis of a severe developmental and neurological disorder associated with a de novo G375R variant of the tetrameric BK channel is unknown. Here, we address this question by recording from single BK channels expressed to mimic a G375R mutation heterozygous with a WT allele. Five different types of functional BK channels were expressed: 3% were consistent with WT, 12% with homotetrameric mutant, and 85% with three different types of hybrid (heterotetrameric) channels assembled from both mutant and WT subunits. All channel types except WT showed a marked gain-of-function in voltage activation and a smaller decrease-of-function in single-channel conductance, with both changes in function becoming more pronounced as the number of mutant subunits per tetrameric channel increased. The net cellular response from the five different types of channels comprising the molecular phenotype was a shift of -120 mV in the voltage required to activate half of the maximal current through BK channels, giving a net gain-of-function. The WT and homotetrameric mutant channels in the molecular phenotype were consistent with genetic codominance as each displayed properties of a channel arising from only one of the two alleles. The three types of hybrid channels in the molecular phenotype were consistent with partial dominance as their properties were intermediate between those of mutant and WT channels. A model in which BK channels randomly assemble from mutant and WT subunits, with each subunit contributing increments of activation and conductance, approximated the molecular phenotype of the heterozygous G375R mutation.

Lymphomas in patients with neurofibromatosis type 1 (NF1): another malignancy in the NF1 syndrome?

Neurofibromatosis type 1 (NF1) is an autosomal dominant multisystem syndrome caused by mutations in the neurofibromin 1 (NF1) gene that encodes for the protein neurofibromin acting as a tumour suppressor. Neurofibromin functions primarily as a GTPase-activating protein for the Ras family of oncogenes, which activates many signalling pathways for cell proliferation and differentiation; without neurofibromin, Ras is constitutively activated, thereby turning on many downstream signalling pathways related to oncogenesis. Patients with NF1 have a well known predisposition for certain types of malignancies including malignant peripheral nerve sheath tumours, gliomas, and breast cancers, as well as a potential association of NF1 with lymphoproliferative disorders such as lymphomas. In this article, we review the pathophysiology and tumourigenesis of NF1, previously reported cases of cutaneous lymphomas in NF1 patients along with our case demonstration of a NF1-associated scalp B-cell lymphoma, and NF1-associated extra cutaneous lymphomas. The diagnosis of lymphomas particularly cutaneous lymphomas may be difficult in NF1 patients as they often have skin lesions and/or cutaneous/subcutaneous nodules or tumours like neurofibromas, which raises the possibility of underdiagnosed cutaneous lymphomas in NF1 patients. We also comprehensively discuss the association between NF1 and lymphomas. In summary, most studies support a potential association between NF1 and lymphomas. Further investigation is needed to clarify the association between NF1 and lymphomas in order to bring clinical awareness of possibly underdiagnosed NF1-associated lymphomas and individualised management of NF1 patients to practice.

Incidental multifocal calcifying pseudoneoplasm of the neuraxis: case report and literature review.

Calcifying pseudoneoplasm of the neuraxis (CAPNON) is thought to be a rare tumefactive lesion with unknown pathogenesis. Its prevalence is questionable with few previously reported cases of incidental CAPNON, and likely underdiagnosis. We report a unique case of incidental multifocal CAPNON. A 64-year-old female was admitted with loss of consciousness due to a ruptured right middle cerebral artery aneurysm with subarachnoid and intraventricular hemorrhage. She has a craniotomy and clipping. At time of operation, numerous small dural-based nodules were found, and one was excised for biopsy and was diagnosed as CAPNON. Retrospective review of her CT images identified nodules that were all ipsilateral to the ruptured aneurysm. A literature review revealed that incidental and/or multifocal CAPNONs are rare but likely underreported. Our case suggests a reactive process in the pathogenesis of CAPNON.

ALK-negative CNS anaplastic large cell lymphoma: case report and review of literature.

BACKGROUND: Central nervous system (CNS) lymphomas frequently pose a diagnostic challenge to physicians. CNS anaplastic large cell lymphoma (ALCL) is a rare condition. A majority (80%) of ALCLs harbour anaplastic lymphoma kinase 1 (ALK-1) mutation with only a minority testing negative for this mutation. METHODS: Here we report a rare case of ALK-negative CNS ALCL with dural involvement. We conducted a literature search using PubMed for published studies in English on cases of patients with ALCL of the brain. The keywords used were 'anaplastic large cell lymphoma', 'ALK' and 'primary central nervous system lymphoma'. RESULTS: A 63-year-old man presents with waxing and waning cranial nerve and spinal cord symptoms. MRI revealed multiple intracranial and intra-spinal lesions that were highly steroid responsive. A wide range of serum and CSF tests were non-diagnostic during three months of workup before a lesion appeared in the cervical spine that required decompression and allowed us to obtain a tissue sample. Final pathology revealed ALK-negative ALCL. There are only 24 reported adult cases to date of CNS ALCL in the English literature. To our knowledge, this is the first case of ALK-negative ALCL with primarily CNS and meningeal involvement. CONCLUSIONS: ALK-negative ALCL with CNS involvement is extremely rare, which frequently results in delayed diagnosis (average 40.5 days). The diagnostic challenge posed by this case highlights the importance of a team approach to workup and diligent patient follow-up for such a rare disease.

Impact of Respiratory Infection and Chronic Comorbidities on Early Pediatric Antibiotic Dispensing in the United States.

BACKGROUND: In the United States, children aged <5 years receive high volumes of antibiotics, which may contribute to antibiotic resistance. It has been unclear what role preventable illnesses and chronic comorbidities play in prompting antibiotic prescriptions. METHODS: We conducted an observational study with a cohort of 124 759 children aged <5 years born in the United States between 2008 and 2013 with private medical insurance. Study outcomes included the cumulative number of antibiotic courses dispensed per child by age 5 and the proportion of children for whom at least 1 antibiotic course was dispensed by age 5. We identified which chronic medical conditions predicted whether a child would be among the top 20% of antibiotic recipients. RESULTS: Children received a mean of 6.8 (95% confidence interval [CI]: 6.7-6.9) antibiotic courses by age 5, and 91% (95% CI: 90%-92%) of children had received at least 1 antibiotic course by age 5. Most antibiotic courses (71%; 95% CI: 70%-72%) were associated with respiratory infections. Presence of a pulmonary/respiratory, otologic, and/or immunological comorbidity substantially increase a child's odds of being in the top 20% of antibiotic recipients. Children with at least 1 of these conditions received a mean of 10.5 (95% CI: 10.4-10.6) antibiotic courses by age 5. CONCLUSIONS: Privately insured children in the United States receive many antibiotics early in life, largely due to respiratory infections. Antibiotic dispensing varies widely among children, with more antibiotics dispensed to children with pulmonary/respiratory, otologic, and/or immunological comorbidities.

Association Between Telemedicine Use in Nonmetropolitan Counties and Quality of Care Received by Medicare Beneficiaries With Serious Mental Illness.

Importance: Access to specialty mental health care remains challenging for people with serious mental illnesses, such as schizophrenia and bipolar disorder. Whether expansion of telemedicine is associated with improved access and quality of care for these patients is unclear. Objective: To assess whether greater telemedicine use in a nonmetropolitan county is associated with quality measures, including use of specialty mental health care and medication adherence. Design, Setting, and Participants: In this cohort study, the variable uptake of telemental health visits was examined across a national sample of fee-for-service claims from Medicare beneficiaries in 2916 nonmetropolitan counties between January 1, 2010, and December 31, 2018. Beneficiaries with schizophrenia and related psychotic disorders and/or bipolar I disorder during the study period were included. For each year of the study, each county was categorized based on per capita telemental health service use (none, low, moderate, and high). The association between telemental health service use in the county and quality measures was tested using a multivariate model controlling for both patient characteristics and county fixed effects. Analyses were conducted from January 1 to April 11, 2022. Before the COVID-19 pandemic, telemedicine reimbursement was limited to nonmetropolitan beneficiaries. Main Outcomes and Measures: Receipt of a minimum of 2 specialty mental health service visits (telemedicine or in-person) in the year, number of months per year with medication, hospitalization rate, and outpatient follow-up visits after a mental health hospitalization in a year. Results: In 2018, there were 2916 counties with 118 170 patients (77 068 [65.2%] men; mean [SD] age, 58.3 [15.6] years) in the sample. The fraction of counties that had high telemental health service use increased from 2% in 2010 to 17% in 2018. In 2018 there were 1.08 telemental health service visits per patient in the high telemental health counties. Compared with no telemental health care in the county, patients in high-use counties were 1.2 percentage points (95% CI, 0.81-1.60 percentage points) (8.0% relative increase) more likely to have a minimum number of specialty mental health service visits, 13.7 percentage points (95% CI, 5.1-22.3 percentage points) (6.5% relative increase) more likely to have outpatient follow-up within 7 days of a mental health hospitalization, and 0.47 percentage points (95% CI, 0.25-0.69 percentage points) (7.6% relative increase) more likely to be hospitalized in a year. Telemental health service use was not associated with changes in medication adherence. Conclusions and Relevance: The findings of this study suggest that greater use of telemental health visits in a county was associated with modest increases in contact with outpatient specialty mental health care professionals and greater likelihood of follow-up after hospitalization. No substantive changes in medication adherence were noted and an increase in mental health hospitalizations occurred.

Transportation capacity shortage influence on logistics performance: evidence from the driver shortage.

The study aims to provide an in-depth analysis of a transportation capacity shortage issue affecting Australian logistics service providers. Transportation capacity shortage is an important issue in all transportation modes. In this study, the driver shortage is viewed as an antecedent variable to estimate the impact of transportation capacity shortage on logistics performance. This study investigates the underlying relationships between driver shortage, logistics capability, and logistics performance according to resource-based theory. Structural equation modeling (SEM) was used to analyze the measurement models and structural model. The empirical results illustrate that driver shortage indirectly influences logistics performance, the logistics capability is a mediator factor in the relationship between driver shortage and logistics performance in logistics service providers. We argue that this provides valuable insights for transportation capacity shortage management.

Exploring Teacher Job Satisfaction in Rural China: Prevalence and Correlates.

Extant research continues to establish the importance of teacher job satisfaction to student performance, yet teacher job satisfaction remains under-investigated in rural China. In this paper, we examine the prevalence and correlates of teacher job satisfaction. Using data from 634 teachers across 120 schools in rural China, we find an alarmingly high prevalence of teacher job dissatisfaction: roughly 21% of rural teachers were less than satisfied with their jobs. In addition, we find that several individual- and school-level characteristics, including being a male teacher, being a homeroom teacher, not having a management role in school, being a middle-aged teacher, and a school's boarding status, are correlated with teacher job dissatisfaction. In sum, the results demonstrate a need for further research and policy interventions to improve teacher job satisfaction in rural schools.

Image-Guided versus Freehand Ventricular Drain Insertion: Systematic Review and Meta-analysis.

BACKGROUND: Ventricular drain insertion is a common neurosurgical procedure, typically performed using a freehand approach. Use of image guidance during drain insertion could improve accuracy and reduce the incidence of drain failure. This review aims to assess the impact of image guidance on drain placement accuracy, failure rate, and number of ventricular cannulation attempts. METHODS: We searched MEDLINE, Embase, and Cochrane Library databases from inception to February 2021 for studies comparing image-guided versus freehand ventricular drain insertion. Two reviewers independently screened studies for eligibility, extracted data, and assessed risk of bias and quality of evidence. Pooled data were reported using random effects model. The ROBINS-I tool was used to assess risk of bias and the GRADE approach was used to assess quality of evidence. RESULTS: Of 1102 studies retrieved, 17 were included for a total of 3404 patients. All included studies were of non-randomized design. Pooled data on drain accuracy and drain failure rates showed favorable effect of image guidance, with risk ratio of 1.31 (95% confidence interval [CI] 1.13-1.51, low quality evidence) and 0.63 (95% CI 0.48-0.83, moderate quality evidence), respectively. Pooled data were equivocal for number of attempts with mean difference score of -0.14 times (95% CI -0.44 to 0.15, very low-quality evidence). Heterogeneity was substantial for drain accuracy and failure rate outcomes. CONCLUSIONS: In patients undergoing ventricular drain insertion, the use of image guidance may enhance drain accuracy and reduce drain failure rate. The use of image guidance probably does not decrease the number of drain insertion attempts.