Sodium Glucose Co-Transporter2 (SGLT2) Inhibition for Refractory Hypomagnesemia in Monogenic Diabetes Type 5 (MODY 5)

Abstract Background: MODY 5 is an infrequently reported form of monogenic diabetes attributed to deletions of chromosome 17q12 with impaired expression of HNF1β (Hepatocyte Nuclear Factor 1 Beta). We report a patient who presented with hyperglycemia and hypomagnesemia with an eventual diagnosis of MODY5 that responded to treatment with the SGLT2 inhibitor (SGLT2i), canagliflozin. Clinical case: A 64-year-old male diagnosed with diabetes at age 60 and treated with glimepiride and metformin (HbA1c 6.1–6.2% without hypoglycemia) presented to establish care. He had a prior history of hypermagnesuric hypomagnesemia (serum Magnesium (Mg) 1.4 ± 0.3 mg/dl with Fractional Excretion of Mg (FEMg) 32 ± 3% [values >3–4% in the setting of normal renal function and hypomagnesemia indicates renal Mg loss]) that developed while taking Triamterene- HCTZ for hypertension, prompting discontinuation. Treatment with oral and intravenous (IV) Magnesium along with Amiloride failed to normalize serum Mg levels. Genetic evaluation revealed 17q12 deletion consistent with a diagnosis of MODY 5. Referral to nephrology resulted in discontinuation of glimepiride and addition of canagliflozin 100 mg titrated to 300 mg daily. Mg levels normalized (serum Mg level 1.9 ± 0.1 mg/dL) within 8 weeks of canagliflozin therapy, allowing discontinuation of IV Mg and patient reported improvement in physical stamina and quality of life. At his 1 year follow up visit, his serum Mg remains stable at 1.8mg/dl with a FEMg of 22 ± 2.5%. His current therapy includes Metformin 2 gm, Canagliflozin 300 mg, Amiloride 10 mg tid, and oral Mg. Discussion: Prior to introduction of the SGLT2i, MODY 5 patients required oral and IV Mg repletion in combination with amiloride to achieve near normal Mg levels. Several clinical trials with SGLT2i demonstrated dose and agent dependent improvement in Mg levels in patients with type 2 diabetes. Proposed explanations include reductions in eGFR, changes in intraluminal electrical potential, and activation of renin angiotensin aldosterone system. Mg replacement results not only in symptomatic improvement, but has also been demonstrated to reduce risk of stroke and all-cause mortality. In summary, SGLT2 inhibitors in patients with MODY 5 can be effective in restoring normal Mg levels, improving quality of life, and reducing all cause mortality.

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Prediction of all-cause mortality from 24 month trajectories in patient-reported psychological, clinical and quality of life outcomes in uveal melanoma patients

Journal of Behavioral Medicine ◽

10.1007/s10865-021-00252-8 ◽

2021 ◽

Author(s):

Stephen L. Brown ◽

Peter L. Fisher ◽

Laura Hope-Stone ◽

Heinrich Heimann ◽

Rumana Hussain ◽

...

Keyword(s):

Quality Of Life ◽

Life Expectancy ◽

Uveal Melanoma ◽

Cox Regression ◽

Multivariate Analyses ◽

Tumor Diameter ◽

Control Variables ◽

Patient Reported ◽

All Cause Mortality

AbstractA number of patient-reported outcomes (PROs) predict increased mortality after primary cancer treatment. Studies, though, are sometimes affected by methodological limitations. They often use control variables that poorly predict life expectancy, examine only one or two PROs thus not controlling potential confounding by unmeasured PROs, and observe PROs at only a single point in time. To predict all-cause mortality, this study used control variables affording good estimates of life expectancy, conducted multivariate analyses of multiple PROs to identify independent predictors, and monitored PROs two years after diagnosis. We recruited a consecutive sample of 824 patients with uveal melanoma between April 2008 and December 2014. PROs were variables shown to predict mortality in previous studies; anxiety, depression, visual and ocular symptoms, visual function impairment, worry about cancer recurrence, and physical, emotional, social and functional quality of life (QoL), measured 6, 12 and 24 months after diagnosis. We conducted Cox regression analyses with a census date of December 2018. Covariates were age, gender, marital and employment status, self-reported co-morbidities, tumor diameter and thickness, treatment modality and chromosome 3 mutation status, the latter a genetic mutation strongly associated with mortality. Single predictor analyses (with covariates), showed 6-month depression and poorer functional QoL predicting mortality, as did 6–12 month increases in anxiety and 6–12 month decreases in physical and functional QoL. Multivariate analyses using all PROs showed independent prediction by 6-month depression and decreasing QoL over 6–12 months and 12–24 months. Elevated depression scores six months post-diagnosis constituted an increased mortality risk. Early intervention for depressive symptoms may reduce mortality.

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226Health-related quality of life and all-cause mortality among older people: a prospective cohort study

International Journal of Epidemiology ◽

10.1093/ije/dyab168.533 ◽

2021 ◽

Vol 50 (Supplement_1) ◽

Author(s):

Aung Zaw Zaw Phyo ◽

Joanne Ryan ◽

David Gonzalez-Chica ◽

John McNeil ◽

Robyn Woods ◽

...

Keyword(s):

Quality Of Life ◽

Short Form ◽

The United States ◽

Community Dwelling ◽

Older Individuals ◽

Patient Reported ◽

All Cause Mortality ◽

Related Quality ◽

Health Related

Abstract Background Health-related quality of life (HRQoL) is a measure of an individual’s self-perceived health status. Few studies have examined HRQoL as a risk factor for mortality. This study examined whether HRQoL predicts all-cause mortality in older community-dwelling individuals from Australia and the United States enrolled in the Aspirin in Reducing Events in the Elderly (ASPREE) trial, and if this association varies across gender. Methods The 19,106 persons aged 65–98 years and free of known major life-limiting disease, who completed the 12-item short form (SF-12) HRQoL at ASPREE-baseline (2010–2014) were followed prospectively until 2017 for all-cause mortality. Cox proportional-hazard models were used to determine the association between the physical (PCS) and mental component scores (MCS) of HRQoL and all-cause mortality, adjusting for sociodemographic factors, health-related behaviours, and clinical measures. Results There were 1,052 deaths over a median 4.7-year of follow-up, with 11.9 events per 1,000 person-years. A 10-unit increase in PCS was associated with a 17% decrease in all-cause mortality (95%CI: 0.77, 0.89). MCS was not associated with all-cause mortality. There was no evidence these associations were different between males and females (P-values for interaction: PCS 0.13 and MCS 0.44). Conclusions PCS, but not MCS, was inversely associated with all-cause mortality in this large cohort of healthy older individuals. Key messages Our findings support the decision of the Australian Commission on Safety and Quality in Health Care to incorporate the SF-12 into the routine collection of Patient Reported Outcome Measures as a policy goal for the Australian health system.

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Benefits and harms of high-dose haemodiafiltration versus high-flux haemodialysis: the comparison of high-dose haemodiafiltration with high-flux haemodialysis (CONVINCE) trial protocol

BMJ Open ◽

10.1136/bmjopen-2019-033228 ◽

2020 ◽

Vol 10 (2) ◽

pp. e033228 ◽

Cited By ~ 1

Author(s):

Peter J Blankestijn ◽

Kathrin I Fischer ◽

Claudia Barth ◽

Krister Cromm ◽

Bernard Canaud ◽

...

Keyword(s):

Quality Of Life ◽

Cost Effectiveness ◽

Cardiovascular Events ◽

Public Health Problem ◽

High Dose ◽

Major Public Health Problem ◽

High Flux ◽

Patient Reported ◽

All Cause Mortality

IntroductionEnd-stage kidney disease (ESKD) is a major public health problem affecting more than 2 million people worldwide. It is one of the most severe chronic non-communicable diseases. Haemodialysis (HD) is the most common therapeutic option but is also associated with a risk of cardiovascular events, hospitalisation and suboptimal quality of life. Over the past decades, haemodiafiltration (HDF) has become available. Although high-dose HDF has shown some promising survival advantage compared to conventional HD, the evidence remains controversial. A Cochrane systematic review found, in low-quality trials, with various convective forms of dialysis, a reduction in cardiovascular, but not all-cause mortality and the effects on non-fatal cardiovascular events and hospitalisation were uncertain. In contrast, an individual patient data analysis suggested that high-dose HDF reduced both all-cause and cardiovascular mortality compared to HD. In view of these discrepant results, a definitive trial is required to determine whether high-dose HDF is preferable to high-flux HD. The comparison of high-dose HDF with high-flux HD (CONVINCE) study will assess the benefits and harms of high-dose HDF versus a conventional high-flux HD in adults with ESKD.Methods and analysisThis international, prospective, open label, randomised controlled trial aims to recruit 1800 ESKD adults treated with HD in nine European countries. Patients will be randomised 1:1 to high-dose HDF versus continuation of conventional high-flux HD. The primary outcome will be all-cause mortality at 3 years’ follow-up. Secondary outcomes will include cause-specific mortality, cardiovascular events, all-cause and infection-related hospitalisations, patient-reported outcomes (eg, health-related quality of life) and cost-effectiveness.Ethics and disseminationThe CONVINCE study will address the question of benefits and harms of high-dose HDF compared to high-flux HD for kidney replacement therapy in patients with ESKD with a focus on survival, patient perspectives and cost-effectiveness.Trial registration numberNetherlands National Trial Register (NTR 7138).

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General Patient-Reported Outcome Measure Tools Non-Reflective of AL Amyloidosis Quality of Life (QoL): A Systematic Literature Review

Blood ◽

10.1182/blood-2021-147021 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 5007-5007

Author(s):

Sotirios Bristogiannis ◽

Charalampia Kyriakou ◽

Ashutosh Wechelaker ◽

Brendan Wisniowski ◽

Shameem Mahmood ◽

...

Keyword(s):

Quality Of Life ◽

Literature Review ◽

Patient Reported Outcome ◽

Current Therapy ◽

Al Amyloidosis ◽

Health Measurement ◽

Sf 36 ◽

Patient Reported ◽

The Impact

Abstract Background: Systemic AL Amyloidosis is characterized by deposition by amyloid fibrils of light chains produced by clonal plasma cells. New combination therapies have substantially prolonged the life expectancy of patients with AL Amyloidosis . Still the prognosis of the disease in the majority of the patients is dismal and Quality of Life (QoL) issues should be included in clinicians' primary objectives. Nowadays, patient-reported outcome measures (PROMs) are considered one of the most responsive tools that can guide personalized interventions to optimize QoL in parallel with therapeutic interventions. The aim of this metanalysis was to establish which PROMs have been utilized in studies on AL Amyloidosis and evaluate their validity. Methods: Two independent investigators (S.B.; C.K.) systemically reviewed PubMed, Medline and EMBASE databases for publications up to May 2021 on PROMs employed to report QoL outcomes in AL Amyloidosis. The identified PROMs were subsequently assessed for their validity in this context against COSMIN (Consensus-based Standards for the selection of health Measurement Instruments) quality criteria. Results: Of the 246 publications originally retrieved, only 57 were further analysed as 92 were duplicates, 11 were irrelevant to AL Amyloidosis, 56 did nor refer to QOL and 13 reported QOL without using QOLQs, 13 were case-reports and 4 were review articles. These included 47 observational studies and 10 prospective clinical trials. In these, thirteen different PROMs were used on occasion to report QOL outcomes (SF-36; EQ-5D-3L; FACT-G; PROMIS-GH); HPRSS; DT; EORTC QLQ-C30; KCCQ-12; GAF; SWLS; STAI; CESD; MDASI) with SF-36 being the most popular (35/ 58 publications). All of them are traditionally validated in similar to AL Amyloidosis diseases (e.g. Multiple Myeloma) or in its complications (e.g. Congestive Heart Failure). In the absence of face-validity studies, the content validity of these PROMs was assessed against QOL aspects identified in literature by open questionnaires (Table 1). The outcome of the intensive analysis of these studies showed that the QoLQ fail to cover the broad spectrum of disease symptoms and current therapy-related toxicity. Furthermore, there is limited if any evidence for the validation of these tools in this context (Table 2). COSMIN criteria were met only for SF-36 and PROMIS-GH as regards internal consistency (Cronbach's a>70). Conclusions: This literature review reveals that commonly applied PROMs in studies on AL Amyloidosis do not represent the impact of this complex disease and its treatment on QoL issues. Thus, there is a need to develop a new, well-validated, disease-specific PROM that can facilitate the approval of new treatments and the adjustment of therapy-intensity according to its toxicity and QoL. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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Association of Physical Morbidity and Health-Related Quality of Life in a Representative Sample of Older German People

European Journal of Health Psychology ◽

10.1027/2512-8442/a000019 ◽

2018 ◽

Vol 25 (4) ◽

pp. 140-151

Author(s):

Markus A. Wirtz ◽

Matthias Morfeld ◽

Elmar Brähler ◽

Andreas Hinz ◽

Heide Glaesmer

Keyword(s):

Quality Of Life ◽

Representative Sample ◽

Short Form ◽

Physical Symptoms ◽

German Population ◽

Health Related Quality ◽

Patient Reported ◽

Related Quality ◽

Health Related

Abstract. The association between health-related quality of life (HRQoL; Short-Form Health Survey-12; SF-12) and patient-reported morbidity-related symptoms measured by the Patient Health Questionnaire-15 (PHQ-15) is analyzed in a representative sample of older people in the general German population. Data from 1,659 people aged 60 to 85 years were obtained. Latent class analysis identified six classes of patients, which optimally categorize clusters of physical symptoms the participants reported: musculoskeletal impairments (39.8%), healthy (25.7%), musculoskeletal and respiratory/cardiac impairments (12.8%), musculoskeletal and respiratory impairments, along with bowel and digestion problems (12.9%), general impairments (4.9%), and general impairments with no bowel and digestion problems (4.8%). The participants’ SF-12 Physical Health Scores (η2 = .39) and their Mental Health Scores (η2 = .28) are highly associated with these latent classes. These associations remain virtually identical after controlling for age. The results provide evidence that profiles of patient-reported physical impairments correspond strongly with reduced HRQoL independently from aging processes.

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