A crossover comparison of patient satisfaction with two teriparatide regimens: primary results of the Japanese Osteoporosis Intervention Trial 06 (JOINT-06).

INTRODUCTION: This study aimed to compare treatment satisfaction with two dosing regimens (two teriparatide [TPTD] self-injection systems) in osteoporosis patients at high risk of fracture. MATERIALS AND METHODS: In this open-label crossover randomized trial comparing self-injected once-daily (1/D)-TPTD with self-injected twice-weekly (2/W)-TPTD, three satisfaction variables were evaluated by questionnaire for 2 years. The primary endpoint was overall satisfaction and secondary endpoints were satisfaction with treatment effectiveness and with utility of the self-injection device. Changes in quality of life (QOL) assessed by EuroQol-5 Dimension, pain assessed by visual analogue scale (VAS), and anthropometric parameters were also analyzed. Safety was evaluated based on the incidence and severity of adverse events (AEs). RESULTS: The 1/D-TPTD and 2/W-TPTD groups consisted of 180 (75.9 ± 7.3 years) and 179 (age: 75.5 ± 6.9 years) patients, respectively. After 26 weeks of treatment, no significant between-group difference in the persistence rate (79.4% vs 72.6% in the 1/D-TPTD and 2/W-TPTD groups, respectively), distributions of overall satisfaction scores, and satisfaction with treatment (p > 0.05) were observed. However, several items of satisfaction with the utility of the injection device were significantly higher in the 2/W-TPTD group (p < 0.05). Statistical improvements from baseline values were observed in QOL and pain VAS in both groups (p < 0.05). No serious AEs were reported. CONCLUSION: The between-group similarity of overall treatment satisfaction and effectiveness scores and between-group difference in satisfaction with the utility of the self-injection device was useful information for real-world treatment of osteoporosis. Both medication regimens were well tolerated.

Comparison of the Continuation Rate of Twice-Weekly and Weekly Teriparatide Administration in a Rural Area.

Teriparatide plays an important role in the treatment of patients with severe osteoporosis; however, it is meaningless if patients cannot continue. In recent years, the use of a twice-weekly auto-injector teriparatide preparation has become possible. However, its continuation rate and the factors affecting it have not been adequately investigated. Therefore, this study aimed to examine the continuation rate of twice-weekly teriparatide and the factors affecting it. This retrospective study included 143 patients who were administered teriparatide weekly (65 patients) or twice-weekly (78 patients) in a rural hospital. Patient information, such as age, the distance between the hospital and home, family structure, past osteoporosis treatment and fracture, adverse events, and period of teriparatide continuation, were collected. We compared the differences in continuation rates between the twice-weekly and the weekly groups using the Kaplan-Meier curves, and we examined factors influencing teriparatide discontinuation using multivariate analyses. The 12- and 24-month continuation rates of twice-weekly administration of teriparatide were 79.5% and 61%, respectively. The twice-weekly group showed a significantly higher continuation rate (P < 0.0001). The multivariate analyses showed that older age and adverse events were identified as risk factors negatively influencing teriparatide continuation (P = 0.0237 and P < 0.0001, respectively). On the other hand, twice-weekly teriparatide was shown to reduce the risk of discontinuation (P = 0.0043). The twice-weekly teriparatide has a considerably higher continuation rate than the weekly teriparatide. Weekly preparation, older age, and adverse event were identified as risk factors negatively influencing teriparatide continuation.

Twice-Weekly Hemodialysis With Adjuvant Pharmacotherapy and Transition to Thrice-Weekly Hemodialysis: A Pilot Study.

RATIONALE & OBJECTIVE: Thrice-weekly hemodialysis (HD) is the most common treatment modality for kidney failure in the United States. We conducted a pilot study to assess the feasibility and safety of incremental-start HD in patients beginning maintenance HD. STUDY DESIGN: Pilot study. SETTING & PARTICIPANTS: Adults with estimated glomerular filtration rate (eGFR) ≥5 mL/min/1.73 m2 and urine volume ≥500 mL/d beginning maintenance HD at 14 outpatient dialysis units. EXPOSURE: Randomized allocation (1:1 ratio) to twice-weekly HD and adjuvant pharmacologic therapy for 6 weeks followed by thrice-weekly HD (incremental HD group) or thrice-weekly HD (conventional HD group). OUTCOME: The primary outcome was feasibility. Secondary outcomes included changes in urine volume and solute clearance. RESULTS: Of 77 patients invited to participate, 51 consented to do so, representing 66% of eligible patients. We randomized 23 patients to the incremental HD group and 25 patients to the conventional HD group. Protocol-based loop diuretics, sodium bicarbonate, and patiromer were prescribed to 100%, 39%, and 17% of patients on twice-weekly HD, respectively. At a mean follow-up of 281.9 days, participant adherence was 96% to the HD schedule (22 of 23 and 24 of 25 in the incremental and conventional groups, respectively) and 100% in both groups to serial timed urine collection. The incidence rate ratio for all-cause hospitalization was 0.31 (95% CI, 0.08-1.17); and 7 deaths were recorded (1 in the incremental and 6 in the conventional group). At week 24, the incremental HD group had lower declines in urine volume (a difference of 51.0 [95% CI, -0.7 to 102.8] percentage points) and in the averaged urea and creatinine clearances (a difference of 57.9 [95% CI, -22.6 to 138.4] percentage points). LIMITATIONS: Small sample size, time-limited twice-weekly HD. CONCLUSIONS: It is feasible to enroll patients beginning maintenance HD into a randomized study of incremental-start HD with adjuvant pharmacotherapy who adhere to the study protocol during follow-up. Larger multicenter clinical trials are indicated to determine the efficacy and safety of incremental HD with longer twice-weekly HD periods. FUNDING: Funding was provided by Vifor Inc. TRIAL REGISTRATION: Registered at ClinicalTrials.gov, identifier NCT03740048.

Twice-weekly teriparatide improves lumbar spine BMD independent of pre-treatment BMD and bone turnover marker levels.

INTRODUCTION: There have been no reports of the effects of baseline lumbar spine bone mineral density (LS-BMD) and bone turnover marker levels on the therapeutic effect of a 28.2-µg teriparatide formulation for twice-weekly use (2/W-TPTD). MATERIALS AND METHODS: An analysis was performed using data from a double-blind, randomized, non-inferiority trial (TWICE study) conducted with patients who received 2/W-TPTD or a 56.5-µg teriparatide formulation for once-weekly use (1/W-TPTD) for 48 weeks. The patients were divided into tertile groups based on baseline LS-BMD, urinary type I collagen cross-linked N-telopeptide (u-NTX), and serum type I procollagen-N-propeptide (P1NP) levels, respectively. Time profiles of these measurements were analyzed. Furthermore, whether a change in P1NP is a predictor for percentage change in BMD was assessed. RESULTS: Across all tertile groups divided based on baseline LS-BMD and levels of bone turnover markers, the LS-BMD increased significantly. The u-NTX level decreased throughout the study period in the high- and middle-u-NTX-level groups. The P1NP level increased after 4 weeks, but subsequently decreased after 12 weeks and thereafter in the high-P1NP-level group; it increased after 4 weeks and subsequently fluctuated near the baseline level in the middle-P1NP-level group. A cut-off value of 12.0 µg/L for change in P1NP after 4 weeks of 2/W-TPTD as a predictor for percentage change in LS-BMD of 3% or more after 48 weeks gave a positive predictive value of 89.6%. CONCLUSION: 2/W-TPTD, just like 1/W-TPTD, improved LS-BMD significantly, regardless of baseline LS-BMD and bone turnover marker levels.

Ultrafiltration Rate, Residual Kidney Function, and Survival Among Patients Treated With Reduced-Frequency Hemodialysis.

RATIONALE & OBJECTIVE: Patients receiving twice-weekly or less-frequent hemodialysis (HD) may need to undergo higher ultrafiltration rates (UFRs) to maintain acceptable fluid balance. We hypothesized that higher UFRs are associated with faster decline in residual kidney function (RKF) and a higher rate of mortality. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 1,524 patients with kidney failure who initiated maintenance HD at a frequency of twice or less per week for at least 6 consecutive weeks at some time between 2007 and 2011 and for whom baseline data for UFR and renal urea clearance were available. PREDICTOR: Average UFR during the first patient-quarter during less-frequent HD (<6, 6-<10, 10-<13, and≥13mL/h/kg). OUTCOME: Time to all-cause and cardiovascular death, slope of decline in RKF during the first year after initiation of less-frequent HD (with slopes above the median categorized as rapid decline). ANALYTICAL APPROACH: Cox proportional hazards regression for time to death and logistic regression for the analysis of rapid decline in RKF. RESULTS: Among 1,524 patients, higher UFR was associated with higher all-cause mortality; HRs were 1.43 (95% CI, 1.09-1.88), 1.51 (95% CI, 1.08-2.10), and 1.76 (95% CI, 1.23-2.53) for UFR of 6 to<10, 10 to<13, and≥13mL/h/kg, respectively (reference: UFR < 6mL/h/kg). Higher UFR was also associated with higher cardiovascular mortality. Baseline RKF modified the association between UFR and mortality; the association was attenuated among patients with renal urea clearance≥5mL/min/1.73m2. Higher UFR had a graded association with rapid decline in RKF; ORs were 1.73 (95% CI, 1.18-2.55), 1.89 (95% CI, 1.12-3.17), and 2.75 (95% CI, 1.46-5.18) at UFRs of 6 to<10, 10 to<13, and≥13mL/h/kg, respectively (reference: UFR < 6mL/h/kg). LIMITATIONS: Residual confounding from unobserved differences across exposure categories. CONCLUSIONS: Higher UFR was associated with worse outcomes, including shorter survival and more rapid loss of RKF, among patients receiving regular HD treatments at a frequency of twice or less per week.

Safely reducing haemodialysis frequency during the COVID-19 pandemic.

BACKGROUND: Patients undergoing haemodialysis (HD) are at higher risk of developing worse outcomes if they contract COVID-19. In our renal service we reduced HD frequency from thrice to twice-weekly in selected patients with the primary aim of reducing COVID 19 exposure and transmission between HD patients. METHODS: Dialysis unit nephrologists identified 166 suitable patients (38.4% of our HD population) to temporarily convert to twice-weekly haemodialysis immediately prior to the peak of the COVID-19 pandemic in our area. Changes in pre-dialysis weight, systolic blood pressure (SBP) and biochemistry were recorded weekly throughout the 4-week project. Hyperkalaemic patients (serum potassium > 6.0 mmol/L) were treated with a potassium binder, sodium bicarbonate and received responsive dietary advice. RESULTS: There were 12 deaths (5 due to COVID-19) in the HD population, 6 of which were in the twice weekly HD group; no deaths were definitively associated with change of dialysis protocol. A further 19 patients were either hospitalised and/or developed COVID-19 and thus transferred back to thrice weekly dialysis as per protocol. 113 (68.1%) were still receiving twice-weekly HD by the end of the 4-week project. Indications for transfer back to thrice weekly were; fluid overload (19), persistent hyperkalaemia (4), patient request (4) and compliance (1). There were statistically significant increases in SBP and pre-dialysis potassium during the project. CONCLUSIONS: Short term conversion of a large but selected HD population to twice-weekly dialysis sessions was possible and safe. This approach could help mitigate COVID-19 transmission amongst dialysis patients in centres with similar organisational pressures.

Intradialytic complications among patients on twice-weekly maintenance hemodialysis: an experience from a hemodialysis center in Eritrea.

BACKGROUND: Twice-weekly maintenance hemodialysis sessions in patients with end stage renal disease are commonly practiced due to economic constraints in developing countries including Eritrea. To ameliorate the paucity of data on the subject, our study aims to shed light on the patterns of intradialytic complications exclusively in patients undergoing twice-weekly hemodialysis in the country. METHODS: A descriptive cross-sectional study was conducted from March 01 to July 31, 2018 at Dialysis Unit of Orotta National Referral Hospital, Asmara, Eritrea in patients with end stage renal disease undergoing twice-weekly hemodialysis. Hemodialysis sessions were assessed for intradialytic complications. Data were fed into and analyzed using Epi-Info and Microsoft Excel. RESULTS: A total of 29 patients were included in the five-month study period. Males were 19 (65.5%) and females were 10 (34.5%). More than half of the patients had diabetes. Out of the total 573 hemodialysis sessions, 176 (30.7%) of them involved one or more intradialytic complication. Hypotension was the most common complication occurring in 10% of the sessions followed by nausea and vomiting (5.24%), hypertension (5.06%), muscle cramps (4.71%), and headache (4.54%). Other complications such as back pain, chest pain, fever, chills and itching occurred in less than 3% of the sessions. There was no death immediately associated with the complications. Half of the intradialytic complications occurred in patients with diabetes. There was a positive correlation between intradialytic hypotension and diabetes, ultrafiltration volume as well as eating during hemodialysis. Use of central line catheter as a vascular access was associated with higher complication rate. CONCLUSION: Twice-weekly hemodialysis for end stage renal disease patients probably has similar intradialytic complications as the "standard" thrice-weekly frequency. Although twice-weekly hemodialysis schedule is certainly unsuitable for some patients, its advantage of preserving residual kidney function can prevent excessive interdialytic weight gain and thus lowering the risk of intradialytic hypotension related with higher ultrafiltration rate. Being the first study in the country on dialysis complications, we recommend further large scale research in the future.

Study of twice-weekly injections of Teriparatide by comparing efficacy with once-weekly injections in osteoporosis patients: the TWICE study.

A 48-week, multicenter, randomized, double-blind, double-dummy, active-controlled, non-inferiority trial (the TWICE study) conducted in Japanese primary osteoporosis patients with a high risk of fractures demonstrated that a 28.2-µg twice-weekly regimen of teriparatide can provide comparable efficacy to a 56.5-µg once-weekly regimen of teriparatide, while also improving safety. INTRODUCTION: While a 56.5-µg once-weekly regimen of teriparatide has high efficacy for osteoporosis, treatment continuation rates are low, with one of the major causes being adverse drug reactions such as nausea or vomiting. The TWICE study was therefore conducted to investigate whether a twice-weekly regimen with 28.2-µg teriparatide can provide comparable efficacy to the 56.5-µg once-weekly regimen while improving safety. METHODS: A 48-week, multicenter, randomized, double-blind, double-dummy, active-controlled, non-inferiority trial was conducted in Japan. Patients with primary osteoporosis aged ≥ 65 years at high risk of fractures (n = 553) were randomly allocated to the 28.2-µg twice-weekly group (n = 277) or the 56.5-µg once-weekly group (n = 276). The primary endpoint was the percentage change in lumbar spine (L2-L4) bone mineral density (BMD) at final follow-up. RESULTS: The percentage changes in lumbar spine (L2-L4) BMD at final follow-up in the 28.2-µg twice-weekly and 56.5-µg once-weekly groups were 7.3% and 5.9%, respectively; the difference (95% confidence interval [CI]) in percentage change was 1.3% (0.400-2.283%). Since the lower limit of the 95% CI was above the pre-specified non-inferiority margin (- 1.6%), non-inferiority of the 28.2-µg twice-weekly group was demonstrated. Adverse drug reactions were significantly less frequent in the 28.2-µg twice-weekly group (39.7% vs 56.2%; p < 0.01); the incidence of major adverse drug reactions was lower, and the number of subjects who discontinued due to adverse drug reactions was less in the 28.2-µg twice-weekly group. CONCLUSIONS: A 28.2-µg twice-weekly regimen of teriparatide can provide comparable efficacy to a 56.5-µg once-weekly regimen while improving safety. CLINICAL TRIAL REGISTRATION: JapicCTI-163477 .

Twice-weekly glucocorticosteroids in infants and young boys with Duchenne muscular dystrophy.

INTRODUCTION: Glucocorticosteroids (GC) are effective in slowing weakness in boys with Duchenne muscular dystrophy (DMD). METHODS: This is a multisite, 1-year, open-label trial of twice-weekly prednisolone (5 mg/kg/dose) in infants/young boys (0.4-2.4 years) with DMD. We compared changes in Bayley III Scales of Infant Development (Bayley-III) with untreated boys followed for 1 year (historical control cohort [HCC]). Twenty-three of 25 participants completed the study. RESULTS: Treated boys gained an average of 0.5 points on the Bayley-III gross motor scaled score (GMSS) compared with the HCC who, on average, declined 1.3 points (P = 0.03). All boys maintained linear growth, and none developed Cushingoid features. Excessive weight gain occurred in 13 of 23 (56%) boys. DISCUSSION: This study provides evidence that twice-weekly GC is well tolerated in infants and young boys with DMD and improves GMSS. Excessive weight gain is a potential risk. Longer follow-up is required to determine whether early GC initiation is feasible in most infants/boys with DMD. Muscle Nerve 59:650-657, 2019.

IHDIP: a controlled randomized trial to assess the security and effectiveness of the incremental hemodialysis in incident patients.

BACKGROUND: Most people who make the transition to renal replacement therapy (RRT) are treated with a fixed dose thrice-weekly hemodialysis réegimen, without considering their residual kidney function (RKF). Recent papers inform us that incremental hemodialysis is associated with preservation of RKF, whenever compared with conventional hemodialysis. The objective of the present controlled randomized trial (RCT) is to determine if start HD with one sessions per week (1-Wk/HD), it is associated with better patient survival and other safety parameters. METHODS/DESIGN: IHDIP is a multicenter RCT experimental open trial. It is randomized in a 1:1 ratio and controlled through usual clinical practice, with a low intervention level and non-commercial. It includes 152 incident patients older than 18 years, with a RRF of ≥4 ml/min/1.73 m2, measured by renal clearance of urea (KrU). The intervention group includes 76 patients who will start with incremental HD (1-Wk/HD). The control group includes 76 patients who will start with thrice-weekly hemodialysis régimen. The primary outcome is assessing the survival rate, while the secondary outcomes are the morbidity rate, the clinical parameters, the quality of life and the efficiency. DISCUSSION: This study will enable to know the number of sessions a patient should receive when starting HD, depending on his RRF. The potentially important clinical and financial implications of incremental hemodialysis warrant this RCT. TRIAL REGISTRATION: U.S. National Institutes of Health, ClinicalTrials.gov . Number: NCT03239808 , completed 13/04/2017. SPONSOR: Foundation for Training and Research of Health Professionals of Extremadura.

Twice-weekly ixazomib in combination with lenalidomide-dexamethasone in patients with newly diagnosed multiple myeloma.

Weekly ixazomib with lenalidomide-dexamethasone (Rd) is feasible and has shown activity in newly diagnosed multiple myeloma (NDMM) patients. This phase 1/2 study (NCT01383928) evaluated the recommended phase 2 dose (RP2D), pharmacokinetics, safety and efficacy of twice-weekly ixazomib plus Rd in NDMM; 64 patients were enrolled across both phases. Patients received twice-weekly oral ixazomib 3·0 or 3·7 mg plus lenalidomide 25 mg and dexamethasone 20 mg (10 mg in cycles 9-16) for up to sixteen 21-day cycles, followed by maintenance with twice-weekly ixazomib alone. No dose-limiting toxicities were reported in cycle 1; the RP2D was 3·0 mg based on overall tolerability across multiple cycles. In 62 evaluable patients, the confirmed overall response rate was 94% (68% ≥very good partial response; 24% complete response). Median progression-free survival was 24·9 months. Responses (median duration 36·9 months for patients receiving the RP2D) deepened during treatment. Grade 3 drug-related adverse events (AEs) occurred in 64% of patients, including: rash, 13%; peripheral neuropathy, 8%; hyperglycaemia, 8%. There were no grade 4 drug-related AEs. Thirteen patients discontinued due to AEs. Twice-weekly ixazomib-Rd offers substantial activity with promising long-term outcomes in NDMM patients but may be associated with greater toxicity compared with weekly ixazomib-Rd in this setting.

The variable target model: a paradigm shift in the incremental haemodialysis prescription.

Background: The recent interest in incremental haemodialysis (HD) is hindered by the current prescription based on a fixed target model (FTM) for the total (dialytic + renal) equivalent continuous clearance (ECC). The latter is expressed either as standard Kt/V (stdKt/V), i.e. the pre-dialysis averaged concentration of urea-based ECC, or EKRc, i.e. the time averaged concentration-based ECC, corrected for volume (V) = 40 L. Accordingly, there are two different targets: stdKt/V = 2.3 volumes per week (v/wk) and EKRc = 13 mL/min/40 L. However, fixing the total ECC necessarily implies perfect equivalence of its components-the residual renal urea clearance (Kru) and dialysis clearance (Kd). This assumption is wrong because Kru has much greater clinical weight than Kd. Here we propose that the ECC target varies as an inverse function of Kru, from a maximum value in anuria to a minimum value at Kru levels not yet requiring dialysis. The aim of the present study was to compare the current FTM with the proposed variable target model (VTM). Methods: The double pool urea kinetic model was used to model dialysis sessions for 360 virtual patients and establish equations predicting the ECC as a function of Kd, Kru and the number of sessions per week. An end-dialysis urea distribution V of 35 L (corresponding to a body surface area of 1.73 m 2 ) was used, so that the current EKRc target of 13 mL/min/40 L could be recalculated at an EKRc 35 value of 12 mL/min/35 L equal to 12 mL/min/1.73 m 2 . The latter also coincides with the maximum value of the EKRc 35 variable target in anuria. The minimum target value of EKRc 35 was assumed to coincide with Kru corrected for V = 35 L (i.e. Krc 35 = 6 mL/min/1.73 m 2 ). The corresponding target for stdKt/V was assumed to vary from 2.3 v/wk at Krc 35 = 0 to 1.7 v/wk at Krc 35 = 6 mL/min/1.73 m 2 . On this basis, the variable target values can be obtained from the following linear equations: target EKRc 35 = 12 - Krc 35 ; target stdKt/V = 2.3 - 0.1 × Krc 35 . Two versions of stdKt/V were considered: the classic version (stdKt/V Gotch ) with Kru at 70%, and the current version (stdKt/V Daug ) with Kru at 100%. Results: The VTM with stdKt/V Gotch produces results very close to those using the FTM with stdKt/V Daug . Once-weekly HD is virtually not allowed by the FTM. In contrast, the VTM allows dialysis to start at Krc 35 ∼5 mL/min/1.73 m 2 on a once-weekly HD schedule, at least in relatively healthy patients; this schedule can be maintained until Krc 35 falls below 4 mL/min/1.73 m 2 , at which point the schedule should be changed to a twice-weekly HD schedule, that, in turn, could be maintained until Krc 35 falls below 2 mL/min/1.73 m 2 . Conclusions: A paradigm shift from the FTM to the VTM in the prescription of incremental HD is proposed, whereby the VTM would allow less frequent treatments at lower Kru, with important clinical and economic implications. This approach is likely to be safe but needs to be confirmed by randomized controlled trials.

Incremental Hemodialysis, Residual Kidney Function, and Mortality Risk in Incident Dialysis Patients: A Cohort Study.

BACKGROUND: Maintenance hemodialysis is typically prescribed thrice weekly irrespective of a patient's residual kidney function (RKF). We hypothesized that a less frequent schedule at hemodialysis therapy initiation is associated with greater preservation of RKF without compromising survival among patients with substantial RKF. STUDY DESIGN: A longitudinal cohort. SETTING & PARTICIPANTS: 23,645 patients who initiated maintenance hemodialysis therapy in a large dialysis organization in the United States (January 2007 to December 2010), had available RKF data during the first 91 days (or quarter) of dialysis, and survived the first year. PREDICTOR: Incremental (routine twice weekly for >6 continuous weeks during the first 91 days upon transition to dialysis) versus conventional (thrice weekly) hemodialysis regimens during the same time. OUTCOMES: Changes in renal urea clearance and urine volume during 1 year after the first quarter and survival after the first year. RESULTS: Among 23,645 included patients, 51% had substantial renal urea clearance (≥3.0mL/min/1.73m(2)) at baseline. Compared with 8,068 patients with conventional hemodialysis regimens matched based on baseline renal urea clearance, urine volume, age, sex, diabetes, and central venous catheter use, 351 patients with incremental regimens exhibited 16% (95% CI, 5%-28%) and 15% (95% CI, 2%-30%) more preserved renal urea clearance and urine volume at the second quarter, respectively, which persisted across the following quarters. Incremental regimens showed higher mortality risk in patients with inadequate baseline renal urea clearance (≤3.0mL/min/1.73m(2); HR, 1.61; 95% CI, 1.07-2.44), but not in those with higher baseline renal urea clearance (HR, 0.99; 95% CI, 0.76-1.28). Results were similar in a subgroup defined by baseline urine volume of 600mL/d. LIMITATIONS: Potential selection bias and wide CIs. CONCLUSIONS: Among incident hemodialysis patients with substantial RKF, incremental hemodialysis may be a safe treatment regimen and is associated with greater preservation of RKF, whereas higher mortality is observed after the first year of dialysis in those with the lowest RKF. Clinical trials are needed to examine the safety and effectiveness of twice-weekly hemodialysis.

Personalising haemodialysis treatment with incremental dialysis for incident patients with end-stage kidney disease: an implementation study protocol.

INTRODUCTION: Incremental dialysis is a personalised dialysis prescription based on residual kidney function that allows for the initial use of shorter duration, less frequent and less intense dialysis. It has been associated with enhanced quality of life and decreased healthcare costs when compared with conventional dialysis. While nephrologists report prescribing incremental dialysis, few dialysis programmes offer a systematic approach in offering and evaluating its use. To move evidence into practice, and in order to improve the safety and quality of providing incremental dialysis care, we have designed an implementation study. This study aims to evaluate the systematic assessment of patients starting facility-based haemodialysis for eligibility for incremental dialysis, and the prescription and monitoring of incremental dialysis treatment. METHODS AND ANALYSIS: A hybrid effectiveness and implementation study design is being used to evaluate the implementation of the programme at dialysis sites in Alberta, Canada. The Reach, Effectiveness, Adoption, Implementation and Maintenance framework will be used to capture individual-level and organisational-level impact of the project. Clinical outcomes related to kidney function will be monitored on an ongoing basis, and patient-reported outcomes and experience measures will be collected at baseline and then quarterly throughout the first year of dialysis. ETHICS AND DISSEMINATION: The study was approved by the Health Research Ethics Board of the University of Alberta. The study is funded by the Strategic Clinical Networks of Alberta Health Services. The study will help answer important questions on the effectiveness of incremental dialysis, and inform the acceptability, adoption, feasibility, reach and sustainability of incremental dialysis within provision of haemodialysis care.

Two-Year Outcomes of Daily and Twice-Weekly Teriparatide Treatment in Postmenopausal Women with Severe Osteoporosis: A Randomized Non-Blinded Prospective Study.

BACKGROUND: The long-term effects of daily teriparatide (D-TPTD) and twice-weekly TPTD (W-TPTD) injections are compared among postmenopausal women with severe osteoporosis. METHODS: A total of 102 patients were enrolled and randomly allocated into two groups for the administration of either D-TPTD or W-TPTD. Treatment efficacy was measured as the percentage change in bone mineral density (ΔBMD) from baseline in the lumbar spine, total hip, and femoral neck. The findings were compared between the two groups. RESULTS: At 24 months after treatment, the persistence rates and medication possession ratios in the D-TPTD and W-TPTD groups were 68.6% and 56.9%, and 87.8% and 92.0%, respectively. The ΔBMD in the lumbar spine, total hip, and femoral neck were 15.6%±10.2%, 5.3%± 6.3%, and 5.5%±6.2%, respectively, in the D-TPTD group; and 9.5%±7.9%, 2.3%±6.2%, and 3.1%±7.4%, respectively, in the W-TPTD group following 24 months of treatment. The ΔBMD of the lumbar spine (p=0.008) at 24 months and total hip (p=0.024) at 18 months differed significantly between the two groups. CONCLUSIONS: D-TPTD administration resulted in a significantly higher BMD in the lumbar spine and total hip, supporting this therapeutic regimen for postmenopausal women with severe osteoporosis.

Incremental versus conventional haemodialysis in end-stage kidney disease: a systematic review and meta-analysis.

Background: Appropriate dialysis prescription in the transitional setting from chronic kidney disease to end-stage kidney disease is still challenging. Conventional thrice-weekly haemodialysis (HD) might be associated with rapid loss of residual kidney function (RKF) and high mortality. The benefits and risks of incremental HD compared with conventional HD were explored in this systematic review and meta-analysis. Methods: We searched MEDLINE, Scopus and Cochrane Central Register of Controlled Trials up to April 2023 for studies that compared the impacts of incremental (once- or twice-weekly HD) and conventional thrice-weekly HD on cardiovascular events, RKF, vascular access complications, quality of life, hospitalization and mortality. Results: A total of 36 articles (138 939 participants) were included in this meta-analysis. The mortality rate and cardiovascular events were similar between incremental and conventional HD {odds ratio [OR] 0.87 [95% confidence interval (CI)] 0.72-1.04 and OR 0.67 [95% CI 0.43-1.05], respectively}. However, hospitalization and loss of RKF were significantly lower in patients treated with incremental HD [OR 0.44 (95% CI 0.27-0.72) and OR 0.31 (95% CI 0.25-0.39), respectively]. In a sensitivity analysis that included studies restricted to those with RKF or urine output criteria, incremental HD had significantly lower cardiovascular events [OR 0.22 (95% CI 0.08-0.63)] and mortality [OR 0.54 (95% CI 0.37-0.79)]. Vascular access complications, hyperkalaemia and volume overload were not statistically different between groups. Conclusions: Incremental HD has been shown to be safe and may provide superior benefits in clinical outcomes, particularly in appropriately selected patients. Large-scale randomized controlled trials are required to confirm these potential advantages.

Incremental Hemodialysis: What We Know so Far.

Traditionally, patients that develop progressive chronic kidney disease in need of kidney replacement therapy are prescribed thrice weekly in-center hemodialysis sessions at the beginning of therapy. This empiric prescription is based on historic trials that were comprised of mostly prevalent patients. Incremental hemodialysis is the process of performing <3 sessions of dialysis per week or limiting dialysis dose by duration at the initial onset of treatment to provide a more gradual transition, mimicking the progressive nature of kidney disease. Adding clearance contributions from residual kidney function is the standard of care with peritoneal dialysis but has not routinely been employed with hemodialysis. Accounting for residual kidney function accompanied by improvement in adjuvant pharmacotherapy, such as newer potassium binding agents and dietary modification, can augment dialytic clearances and allow for an incremental approach. Utilizing incremental dialysis has been associated with both preserving residual kidney function as well as improving patient quality of life. Barriers to this approach include concerns regarding patient acceptance of dialysis prescription changes, adherence to therapy, and provider factors that would require a restructuring of the current thrice weekly hemodialysis rubric. Candidacy for incremental therapy has shown the best outcomes when urea clearances exceed 3 mL/min and urine volumes are >500 mL/day, although these measures have been deemed conservative. A significant amount of retrospective and registry data has been supportive of initiating incremental hemodialysis and several pilot studies have shown the feasibility of implementing such an approach. Larger, randomized control trials are needed to fully evaluate safety and efficacy to allow for more widespread acceptance of this patient-centered approach to chronic kidney disease.

Phosphate Intake and Removal in Predominantly Vegetarian Patients on Twice-Weekly Hemodialysis.

Background: Hyperphosphatemia is linked to increased mortality and morbidity in patients on hemodialysis. Currently, the phosphate intake and dialytic removal in predominantly vegetarian patients on twice-weekly dialysis is not well studied. Materials and methods: This prospective, study recruited patients on twice-weekly dialysis of at least 3 months duration. Baseline clinical variables were measured. Dietary protein and phosphorus intake was assessed using a validated food frequency questionnaire. Phosphate binder use was assessed, hourly blood was collected for serum phosphorus during dialysis, and spent dialysate was collected to estimate cumulative phosphorus removal during the session. Results: Forty (67%) of the 60 patients studied were vegetarians. Twenty-eight (48%) were hyperphosphatemic, and 15 (25%) had serum parathormone (PTH) >500 pg/ml. The mean phosphorus intake was 1247 (±312) mg/day, the mean serum phosphorus was 5.49 (±2.01) mg/dl, and the mean dialytic phosphorus removal was 910 (±383) mg/session. Up to 67% of the study population took calcium-based phosphate binders, 25% took sevelamer carbonate, and 40% took activated vitamin D preparation. The lowest tertiles of phosphorus intake correlated with low energy-adjusted protein intake and hypoalbuminemia. Hyperphosphatemic subjects had better nutritional indices (mid-upper arm circumference and body mass index). Dietary intake and serum phosphorus levels were not mutually associated, but both were strongly correlated with total phosphorus removal in the spent dialysate. Serum phosphorus levels fell by 32% by thefirst hour of hemodialysis. Conclusion: Twice-weekly dialysis is often practised in resource-limited Asian countries. However, due to a predominantly vegetarian diet, hyperphosphatemia was noted only in up to half of the patients, despite twice-weekly hemodialysis schedules. This reinforces the fact that plant-based dietary phosphate is less well absorbed.

Effects of Intermittent Fasting on Cardiometabolic Health: An Energy Metabolism Perspective.

This review summarizes the effects of different types of intermittent fasting (IF) on human cardiometabolic health, with a focus on energy metabolism. First, we discuss the coordinated metabolic adaptations (energy expenditure, hormonal changes and macronutrient oxidation) occurring during a 72 h fast. We then discuss studies investigating the effects of IF on cardiometabolic health, energy expenditure and substrate oxidation. Finally, we discuss how IF may be optimized by combining it with exercise. In general, IF regimens improve body composition, ectopic fat, and classic cardiometabolic risk factors, as compared to unrestricted eating, especially in metabolically unhealthy participants. However, it is still unclear whether IF provides additional cardiometabolic benefits as compared to continuous daily caloric restriction (CR). Most studies found no additional benefits, yet some preliminary data suggest that IF regimens may provide cardiometabolic benefits in the absence of weight loss. Finally, although IF and continuous daily CR appear to induce similar changes in energy expenditure, IF regimens may differentially affect substrate oxidation, increasing protein and fat oxidation. Future tightly controlled studies are needed to unravel the underlying mechanisms of IF and its role in cardiometabolic health and energy metabolism.

Is Twice-weekly Maintenance Hemodialysis Justified?

BACKGROUND: The benefits of twice-weekly dialysis at initiation are significant with respect to access longevity, preservation of residual renal function, economic factors, and patient quality of life. It is widely practiced in developing countries due to resource and financial constraints. We present a 3-year follow-up of patients on twice-weekly dialysis and their outcomes. MATERIAL AND METHODS: This was a 3-year observational follow-up study of patients initiated on twice-weekly hemodialysis. Adequacy and basic cost-effective hematological and biochemical parameters were studied monthly. In case of complications, the patient was shifted to thrice-weekly hemodialysis. RESULTS: 88 incident hemodialysis patients were followed up. Total sessions of hemodialysis (HD) studied were 16,406. The mean hemoglobin level was 9.53 g/dl with hyperphosphatemia in 74.88% patients. The mean residual renal function (RRF) at initiation was 5.71 +/- 3.70 ml/min. The mean interdialytic weight gain was 1.91 +/- 1.26 kg with a mean ultrafiltration of 2600 ± 410 ml. The spKt/V and eKt/V were adequate in 68.54% and 48.34% patients; however, the standard Kt/V of 2 was achieved in only 10.51% patients. Emergency HD was done in 41 sessions (0.24%). There were 24 deaths (27.27%) during this period with the mean time to mortality being 503.12 +/- 296.62 days. CONCLUSION: Initiation at twice-weekly schedules for patients on maintenance hemodialysis is a viable option with increments in case of requirement, more so in patients with good urine output and residual renal function. The biochemical and hematological parameters were stable and within KDOQI guidelines and do not worsen with time.