Cost-effectiveness of virtual reality and wet laboratory cataract surgery simulation.

PURPOSE: To evaluate the cost-effectiveness of phacoemulsification simulation training in virtual reality simulator and wet laboratory on operating theater performance. METHODS: Residents were randomized to a combination of virtual reality and wet laboratory phacoemulsification or wet laboratory phacoemulsification. A reference control group consisted of trainees who had wet laboratory training without phacoemulsification. All trainees were assessed on operating theater performance in 3 sequential cataract patients. International Council of Ophthalmology Surgical Competency Assessment Rubric-phacoemulsification (ICO OSCAR phaco) scores by 2 masked independent graders and cost data were used to determine the incremental cost-effectiveness ratio (ICER). A decision model was constructed to indicate the most cost-effective simulation training strategy based on the willingness to pay (WTP) per ICO OSCAR phaco score gained. RESULTS: Twenty-two trainees who performed phacoemulsification in 66 patients were analyzed. Trainees who had additional virtual reality simulation achieved higher mean ICO OSCAR phaco scores compared with trainees who had wet laboratory phacoemulsification and control (49.5 ± standard deviation [SD] 9.8 vs 39.0 ± 15.8 vs 32.5 ± 12.1, P < .001). Compared with the control group, ICER per ICO OSCAR phaco of wet laboratory phacoemulsification was $13,473 for capital cost and $2209 for recurring cost. Compared with wet laboratory phacoemulsification, ICER per ICO OSCAR phaco of additional virtual reality simulator training was US $23,778 for capital cost and $1879 for recurring cost. The threshold WTP values per ICO OSCAR phaco score for combined virtual reality simulator and wet laboratory phacoemulsification to be most cost-effective was $22,500 for capital cost and $1850 for recurring cost. CONCLUSIONS: Combining virtual reality simulator with wet laboratory phacoemulsification training is effective for skills transfer in the operating theater. Despite of the high capital cost of virtual reality simulator, its relatively low recurring cost is more favorable toward cost-effectiveness.

Directly Acting Antivirals for COVID-19: Where Do We Stand?

The outbreak of a novel coronavirus (SARS-CoV-2) in Wuhan, China in December 2019 has now become a pandemic with no approved therapeutic agent. At the moment, the genomic structure, characteristics, and pathogenic mechanisms of SARS-CoV-2 have been reported. Based upon this information, several drugs including the directly acting antivirals have been proposed to treat people with coronavirus disease 2019 (COVID-19). This rapid review aims to describe the directly acting antivirals that have been examined for use in the management of COVID-19. Searches were conducted in three electronic databases, supplemented with a search on arXiv, bioRxiv, medRxiv, ChinaXiv, ClinicalTrials.gov, and Chinese Clinical Trial Registry for studies examining the use of antivirals in COVID-19 to identify for case reports, case series, observational studies, and randomized controlled studies describing the use of antivirals in COVID-19. Data were extracted independently and presented narratively. A total of 98 studies were included, comprising of 38 published studies and 60 registered clinical trials. These drugs include the broad spectrum antivirals such as umifenovir, protease inhibitors such as lopinavir/ritonavir as well as the RNA-dependent RNA polymerase inhibitors, remdesivir, and favipiravir. Other drugs that have been used include the nucleosidase inhibitors and polymerase acidic endonuclease inhibitors which are currently approved for prevention of influenza infections. While some of the drugs appear promising in small case series and reports, more clinical trials currently in progress are required to provide higher quality evidence.

[Diffusive and convective treatments in the clinical practice: observation study of the Pavia district nephrology group]. / Trattamenti diffusivo e convettivo nella pratica clinica: studio osservazionale del gruppo nefrologico pavese.

UNLABELLED: PURPOSE. Although convective treatments are widely used, there is no evidence that they can improve patient survival or hospitalizations nor clinical criteria indicating which patients could benefit from them. This study was carried out to evaluate the dialysis modality distribution and the clinical criteria used in choosing the dialysis therapy by the four dialysis Centers in the district of Pavia, a district characterized by a quite homogeneous population. METHODS: We evaluated age, gender, body mass index (BMI), time on dialysis, number of sessions per week, dialysis duration, dialysis modality, criteria used in choosing dialysis therapy, vascular access (VA), Kt/V, and the number of hypotensive episodes. RESULTS: Two hundred and seventy-two patients were enrolled in the study. Mean age was 67.3 +/- 12 yrs, BMI was 26.3 +/- 6.1, dialytic age was 5.49 +/- 5.5 yrs, Kt/V was 1.4 +/- 0.3, mean session time was 238 min. Fifty-two patients (19.2%) were on a convective treatment. Age, BMI, time on dialysis, dialysis duration and number of sessions per week were no different between convective treatment patients and diffusive treatment patients. Kt/V was significantly different between convective and diffusive methods (1.55 +/- 0.37 vs 1.4 +/- 0.28, p<0.05). Convective treatments were prescribed for cardiovascular (CV) instability by the nephrologists from the Pavia district in the majority of patients (90.9%). There was no difference in hypotensive episodes between convective and diffusive methods. CONCLUSIONS: Our study demonstrated that lacking clinical evidence indicating an improvement in the long-term outcome with convective techniques, nephrologists in the Pavia district choose this type of dialysis treatment to ameliorate CV stability in uremic patients.

Enhanced LDL oxidation in uremic patients: an additional mechanism for accelerated atherosclerosis?

Since oxidized low-density lipoprotein (LDL) is more atherogenic than native LDL, LDL oxidation was investigated in uremic patients who often develop accelerated atherogenesis. Three groups of uremic patients were studied (10 on predialysis conservative therapy, 11 on repetitive hemodialysis, 13 on peritoneal dialysis) and compared with seventy matched controls. LDL oxidation was evaluated in all patients as: (i) the susceptibility to in vitro oxidation (by measuring the resistance to Cu(++)-induced formation of conjugated dienes), (ii) vitamin E concentration in LDL, and (iii) presence of plasma anti-oxidized LDL antibodies, expressed as the ratio anti-oxLDL/anti-nativeLDL antibodies. The lipid profile was studied in all patients. Vitamin E concentration did not differ between the various groups, although LDL from uremic patients appeared more susceptible to in vitro and in vivo oxidation (as demonstrated by an earlier generation of conjugated dienes and by the presence of an higher antibody ratio) compared to control subjects. Subclass analysis of the different patients revealed that peritoneal dialysis treatment ameliorated the oxidation markers. However, a prolonged dialytic treatment caused a decrease in vitamin E concentration in LDL and increased their susceptibility to oxidation.

High- and low-flux acetate-free biofiltration: experimental assessment of calcium mass balance and intact parathyroid hormone behaviour.

We studied total calcium mass balance and plasma intact parathyroid hormone behaviour in 10 uraemic patients who underwent acetate-free biofiltration carried out in accordance with six different dialytic schedules, where either a polyacrylonitrile or a polysulphone membrane was used. Schedules 1 and 2 involved a reinfusion flow rate of 33.3 ml/min with a dialysate calcium concentration (DCa) of 1.75 and 2 mmol/l respectively; in schedule 3, 4, 5 and 6 reinfusion flow rate amounted to 50 ml/min and DCa was respectively of 1.75, 2, 2.25 and 2.5 mmol/l. Dehydration remained unchanged in all schedules: 700 g/h. Finally high- and low-flux acetate-free biofiltration are able to induce different Ca mass balance which may suit different therapeutic contexts. Ca mass balance was either positive or negative depending on reinfusion flow rate and DCa. With a reinfusion flow rate of 33.3 ml/min a DCa of at least 2 mmol/l was necessary to obtain a positive mass balance, while with a reinfusion flow rate of 50 ml/min DCa had to equal 2.25 mmol/l. In high-flux acetate-free biofiltration, the estimation of predialytic Ca2+ and DCa values, using a simple formula, allows prediction of the mass balance that will be attained. At the end of acetate-free biofiltration, intact parathyroid hormone always decreased when a polyacrylonitrile membrane was employed while it increased, in the presence of negative Ca mass balance with a polysulphone membrane.

Calcium mass balance and behavior of intact immunoreactive parathyroid hormone in acetate-free biofiltration: acute and one-year evaluation.

The present study evaluated calcium mass balance (MB) during acetate-free biofiltration (AFB) with a dialysate calcium concentration of 2 mmol/l and different ultrafiltration rates (UF; 42.5 ml/min in schedule 1 and 48.5 ml/min in schedule 3), and with a calcium concentration of 1.75 mmol/l but an UF of 43 ml/min (schedule 2). We also examined the effects of these schedules on the behavior of intact parathyroid hormone (I-PTH). AFB according to schedule 1 and 3 achieve a positive calcium MB (8.49 +/- 1.56 and 5.59 +/- 1.06 mmol, respectively), while in schedule 2 calcium MB merely balanced (0.07 +/- 2.29 mmol/l). A significant acute intradialytic I-PTH decrease was observed with all schedules; after 1 month, however, predialytic PTH values were unchanged in schedules 1 and 3, but worsening was noted in schedule 2. Subsequently, AFB was performed for 12 months employing a dialytic schedule (No. 1) involving a positive calcium balance. A year later I-PTH was significantly lower, thus proving that AFB may play an additional part in controlling secondary hyperparathyroidism.

Long-term effect of oral calcitriol single weekly pulse in CAPD and in HD.

This study was undertaken to evaluate the long-term effect of single weekly oral pulse calcitriol therapy (0.05 mcg/kg) in 16 uremic patients. Eight (5 female, 3 male; aged 51.6 +/- 8.5 years) were on continuous ambulatory peritoneal dialysis (CAPD) for 28.8 +/- 12.7 months with basal intact parathyroid hormone (iPTH) 247 +/- 60 pg/mL. Eight (6 female, 2 male; aged 53 +/- 17.9 years) were on hemodialysis (HD) for 76.3 +/- 55 months with basal iPTH 270.9 +/- 92. Calcium dialysate was 1.75 mmol/L in all patients and serum phosphorus was controlled with CaCO3 2-4 g/day. Ca and P were measured weekly; iPTH and alkaline phosphatase were measured monthly. After two months, iPTH decreased to 132.4 +/- 89 (p < 0.05 vs basal values) in the HD patients and to 158.2 +/- 61 (p < 0.05) in the CAPD group. After six months, iPTH decreased to 108.6 +/- 73.2 (p < 0.01) in the HD patients and to 126.5 +/- 48 (p < 0.01) in the CAPD patients. Two patients (1 HD and 1 CAPD) who were not compliant with phosphate binder therapy were dropped. To control hyperphosphatemia in 1 HD patient we reduced bolus to 0.03 mcg/kg. Two CAPD patients presented hypercalcemia and required calcium dialysate of 1.25 mmol/L. In conclusion, single weekly oral pulse of calcitriol appears to be effective in suppressing mild hyperparathyroidism both in CAPD and in HD patients, even though some variations in the protocols may be required.

Low-density lipoprotein oxidation and antioxidized LDL antibodies in peritoneal dialysis patients.

Due to the potential atherogenic effects of oxidized low-density lipoproteins (LDLs), LDL oxidation was studied in a group of uremic patients on chronic peritoneal dialysis. The results were compared with those obtained in a group of 70 controls, 10 uremic patients on predialytic conservative therapy, and 11 patients on repetitive hemodialysis. LDL oxidation was evaluated in all subjects as the susceptibility to in vitro oxidation (monitoring the resistance to Cu(2+)-induced formation of conjugated dienes, lag-phase minutes) and the presence of plasma antioxidized LDL antibodies, expressed as the ratio anti-ox-LDL/antinative LDL antibodies. Vitamin E (main antioxidant agent) content in LDLs was also measured and the lipid profile studied. No significant changes in vitamin E concentration were found, although LDLs from uremic patients appeared more susceptible to in vitro and in vivo oxidation (as demonstrated by an earlier production of conjugated dienes and by the presence of a higher antibody ratio), as compared to control subjects. Analysis of the different groups of uremic patients revealed that peritoneal dialysis, not hemodialysis, significantly ameliorated the oxidation markers. However, prolonged treatment with peritoneal dialysis caused a decrease in vitamin E concentration in LDLs and increased their susceptibility to oxidation.

Acute effects of repetitive hemodialysis on circulating immunoreactive parathyroid hormone levels in uremic patients undergoing vitamin D (calcitriol) therapy.

The acute effects on parathyroid gland activity of repetitive hemodialysis with a dialysate calcium concentration of between 3.5 and 4 mEq/l were evaluated in 21 hemodialysis patients on calcitriol therapy for 1 year or more. In this study circulating immunoreactive parathyroid hormone (iPTH) levels were measured using radioimmunoassay specific for C-terminal iPTH (C-PTH), middle molecule iPTH (MM-PTH) and intact iPTH (I-PTH), before the dialysis session at the end of the week (I), after 4 h regular hemodialysis (II) and after a further 72 h (III). C-PTH was abnormally high (202 +/- 64 pmol/l) (I) in 18 patients with no documented parathyroid hyperplasia and showed no significant difference in subsequent controls. MM-PTH was also high (379 +/- 125.5 pmol/l) (I), but decreased to 348 +/- 136.7 (II) (p less than 0.05) and returned to predialysis levels (III). I-PTH (I) was 8.2 +/- 5.3 pmol/l (normal levels in 8 patients), fell to 3.4 +/- 2.6 pmol/l (II) (p less than 0.01), and increased (p less than 0.01) with respect to the basal levels of 11.1 +/- 7.5 pmol/l (III). Three patients presented echographically documentable parathyroid hyperplasia and, despite constantly high iPTH levels, showed a similar I-PTH behavior while MM-PTH and C-PTH revealed no constant pattern. The decrease in iPTH levels was accompanied by a significant increase in total calcium and ionized calcium during the hemodialysis session. No significant changes in iCa and Ca together with I-PTH levels were found in 4 volunteers before and after the hemodialysis session with dialysate calcium 2.75 mEq/l. We conclude that I-PTH assay has been shown to capture acute changes in parathyroid gland activity in hemodialyzed patients for both low and high iPTH levels. High calcium dialysate hemodialysis inhibits acutely intradialytic PTH secretion but the effect is just temporary and the 72-hour interdialytic period, despite vitamin D therapy, stimulates parathyroid secretion significantly. Nevertheless, I-PTH fluctuations occur in some patients within the normal range, and high dialysate and calcitriol therapy seem to be capable of controlling parathyroid activity; as regards the remaining population, we suggest that a personalized therapeutic approach should be studied with a view to achieving a better control of interdialytic calcium homeostasis.