Comparative effectiveness and cardiovascular safety of abaloparatide and teriparatide in postmenopausal women new to anabolic therapy: A US administrative claims database study.

Real-world evidence on the comparative effectiveness and safety of abaloparatide versus teriparatide in women with osteoporosis may help inform treatment decisions. Following 18 months of treatment, abaloparatide was comparable to teriparatide for prevention of nonvertebral fractures, resulted in a 22% risk reduction for hip fractures, and demonstrated similar cardiovascular safety. Osteoporotic fracture risk can be reduced with anabolic or antiresorptive medications. In addition to efficacy and safety data from controlled clinical trials, real-world evidence on comparative effectiveness and safety may help inform treatment decisions. INTRODUCTION: The real-world effectiveness of abaloparatide versus teriparatide on nonvertebral fracture (NVF) incidence and cardiovascular safety during the 19-month period after treatment initiation were evaluated (NCT04974723). METHODS: Anonymized US patient claims data from Symphony Health, Integrated Dataverse (IDV)®, May 1, 2017 to July 31, 2019, included women aged ≥ 50 years with ≥ 1 prescription of abaloparatide or teriparatide and no prior anabolic therapy. Most were enrolled in commercial and Medicare health plans. Index was the date of the initial prescription dispensed during the identification period. In 1:1 propensity score matched cohorts, time to first NVF following index date, major adverse cardiovascular events (MACE), and MACE + heart failure (HF) were compared between cohorts using a Cox proportional hazards model. RESULTS: Propensity score matching yielded 11,616 patients per cohort. Overall median age (interquartile range) was 67 (61, 75) years, and 25.6% had a fracture history. Over 19 months, 335 patients on abaloparatide and 375 on teriparatide had a NVF (hazard ratio [95% confidence interval]: 0.89 [0.77, 1.03]), and 121 and 154 patients, respectively, had a hip fracture [HR (95% CI): 0.78 (0.62, 1.00)]. The MACE and MACE + HF rates were similar between cohorts. CONCLUSIONS: Following 18 months of treatment, abaloparatide was comparable to teriparatide for prevention of NVF and similar cardiovascular safety was demonstrated between cohorts.

Gaucher disease: A cause of massive splenomegaly in a 15-year-old black African male.

Patients with Gaucher disease (GD), a rare autosomal recessive lysosomal storage disease, commonly present to paediatricians with massive splenomegaly. While the diagnosis and management of patients with this chronic multisystem disorder has evolved significantly in recent years, the initial diagnosis represents a challenge. We describe the case of a 15-year-old black African male who presented with abdominal distension, delayed growth and fatigue. Initial laboratory studies revealed severe anaemia (haemoglobin concentration 8 g/dL) and moderate thrombocytopenia (platelet count 80 × 109/L). A computed tomography scan of the abdomen showed an enlarged liver of 173 mm and massive splenomegaly of 27 mm. The diagnosis of GD was confirmed by reduced beta-glucocerebrosidase activity and heterozygous mutations in the GBA1 gene. The patient was managed at a dedicated paediatric haematology unit with enzyme replacement therapy and regular clinical, biochemical and radiological monitoring.

Baseline characteristics of 32 patients with Gaucher disease who were treated with imiglucerase: South African data from the International Collaborative Gaucher Group (ICGG) Gaucher Registry.

BACKGROUND: Gaucher disease (GD) is a rare inherited autosomal recessive metabolic disorder with a prevalence in the general population of ~1 per 100 000. To optimise the recognition, diagnosis and management of patients with GD in South Africa (SA), it is important to have an understanding of local patterns of presentation of the disease. OBJECTIVES: To describe the baseline pretreatment characteristics of the SA cohort of patients enrolled into the International Collaborative Gaucher Group (ICGG) Gaucher Registry whowere treated with imiglucerase (Cerezyme; Sanofi Genzyme). METHODS: The ICGG Gaucher Registry is an observational, longitudinal, international database that tracks the clinical, demographic, genetic, biochemical and therapeutic characteristics of patients with GD globally, irrespective of disease severity, treatment status or treatment choice. The study population included all SA patients reported in the ICGG Gaucher Registry as of 1 May 2020. RESULTS: The registry included 49 SA GD patients, of whom 32 received imiglucerase as first primary GD therapy. All the patients had GD type 1, 59.4% were female, and mean and median ages at diagnosis were 14.7 and 9.8 years, respectively. The most common genotype was N370S/N370S (37.5%). At treatment initiation, 30.0% of patients had been splenectomised. Among patients for whom data were available, anaemia was present in one-third of non-splenectomised patients and 12.5% of those with splenectomy, and moderate or severe thrombocytopenia was reported in two-thirds of non-splenectomised patients. Bone pain was present in 30.8% and 57.1% of non- splenectomised and splenectomised patients, respectively. No bone crises were reported, and data relating to other bone complications were available for only ≤3 patients. CONCLUSIONS: Haematological findings and bone pain in this group are similar to those in the global ICGG Gaucher Registry cohort. Lack of baseline data for other bone complications limits interpretation in that regard. Clinicians who treat patients with GD are encouraged to submit accurate, complete and up-to-date information so that comprehensive data for the subset of SA GD patients can be maintained to improve recognition and diagnosis, and guide appropriate and effective use of treatment for SA patients.

Palivizumab Prophylaxis among Infants at Increased Risk of Hospitalization due to Respiratory Syncytial Virus Infection in UAE: A Hospital-Based Study.

Background: Respiratory syncytial virus (RSV) represents a significant public health burden and the leading cause of lower respiratory tract infections globally, and it is the major cause of hospitalization during the winter. We aimed to evaluate the effectiveness of palivizumab prophylaxis to reduce the hospitalization in children at high risk of RSV infection. Methods: We performed a retrospective observational single-arm hospital-based study including five RSV seasons (September to March) from 2012 to 2017. We retrospectively included premature infants born at less than 35 weeks of gestation with chronic lungs disease or hemodynamic significant congenital heart disease for palivizumab prophylaxis against RSV infection according to the criteria presented. Results: A total of 925 children were enrolled in the study over the five RSV seasons. Of them, 410 (44.3%) infants born at <32 weeks of gestation and 515 (55.6%) infants born at 32-35 weeks of gestation with mean (±SD) birth weight of 1104.8 ± 402.85 and 1842.5 ± 377.5, respectively. The compliance with the course of palivizumab was reported in 841 (90.9%) children. Of them, about 75 (8.9%) hospitalized children were reported, and 17 (2.02%) RSV positive children were detected. Hospitalization due to RSV infection was decreased from 9.23% in the 2012-2013 season to 0.67% in the 2016-2017 season. Conclusion: This study demonstrated that palivizumab prophylaxis in children at high risk of developing RSV infection was effective in reducing the risk of hospitalization with a high compliance rate over the five RSV seasons.

Relationship of Creatinine and Cystatin C-based Estimated Glomerular Filtration rates with Measured Glomerular Filtration Rate in Healthy Kidney Donors from South Asia.

Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation is currently recommended for the estimation of glomerular filtration rate (GFR). This retrospective study aimed to evaluate the correlation between creatinine and cysC-based estimated GFRs and measured GFR in healthy adults. Consecutive healthy adults who were accepted as voluntary kidney donors at our center between January 2008 and December 2012 were included in the study. The 336 individuals who comprised the study population had a mean age of 41.6 ± 11.8 years, male:female ratio 1:1.7, mean creatinine 0.9 ± 0.1 mg/dl, and mean cysC 0.8 ± 0.1 mg/dl. Mean measured GFR by Tc-99m diethylenetriaminepentaacetic acid using Gates method was 98.4 ± 21.2 ml/min/1.73 m2. The mean ± standard deviation of eGFRs by various formulae were as follows: Cockcroft-Gault (CG) = 88.1 ± 15.9 ml/min/1.73 m2, Modification of Diet in Renal Disease (MDRD) = 78 ± 14.7 ml/min/1.73 m2, CKD-EPI creatinine = 88.1 ± 15.5 ml/min/1.73 m2, CKD-EPI cysC = 97 ± 19.9 ml/min/1.73 m2, CKD-EPI creatinine-cysC (CKD-EPI cr-cysC) = 92.5 ± 14.1 ml/min/1.73 m2. The CKD-EPI cr-cysC equation had the highest accuracy, with 43% and 72% of values lying within ±10% and ±20% of the measured GFR, respectively. Bland-Altman analyses for levels of agreement showed least bias with CKD-EPI cysC overall and among females, while among males, CKD-EPI creatinine equation had the least bias. The CKD-EPI equation showed a higher performance than the MDRD and CG equation in GFR estimation of a healthy population. Among CKD-EPI equations, CKD-EPI cr-cysC had the highest accuracy and CKD-EPI cysC the least bias.

Hemostatic Abnormalities in Severe Renal Failure: Do They Bark or Bite?

Abnormal primary hemostasis is believed to be the most significant contributor to uremic bleeding. This study aimed to describe the prevalence and profile of primary and secondary hemostatic disorders in patients with chronic kidney disease (CKD) Stages 4 and 5 and to determine their association if any, with degree of uremia. Stages 4 and 5 predialysis CKD patients attending nephrology outpatient clinic were prospectively recruited and the following bleeding parameters were measured in all patients: platelet count, bleeding time (BT), Factor VIII assay, von Willebrand factor antigen (vWF:Ag), vWF:ristocetin cofactor activity (vWF:RCo), ratio of vWF:ristocetin cofactor activity to vWF antigen (vWF:RCo/vWF:Ag), prothrombin time (PT), and activated partial thromboplastin time (aPTT). Forty-five patients (80%, males) with a mean age of 39.4 years, 82% (n = 37) in Stage 5 CKD, were recruited for the study. The prevalence of thrombocytopenia was significantly higher among patients from West Bengal (15/26, 57.7%) compared to other study patients (2/19, 10.5%; P = 0.001); however, all had macrothrombocytes with normal BT, suggestive of the Harris syndrome. Factor VIII, vWF:Ag, vWF:RCo, vWF:RCo/vWF:Ag ratio, BT, PT, and aPTT were abnormal in 0 (0%), 0 (0%), 0 (0%), 4 (8.8%), 1 (2.2%), 7 (15.6%), and 5 (11.1%) patients, respectively. Except for thrombocytopenia, the prevalence of hemostatic abnormalities did not differ between CKD Stages 4 and 5. Hemostatic abnormalities are uncommon in Stages 4-5 CKD and except for thrombocytopenia, are not associated with degree of uremia. Constitutional macrothrombocytopenia is associated with normal BT even in CKD.

Effect of Double Filtration Plasmapheresis on Various Plasma Components and Patient Safety: A Prospective Observational Cohort Study.

Double filtration plasmapheresis (DFPP) was historically used for blood group incompatible renal transplantation. Very few studies are available worldwide regarding its efficiency in removing specific plasma components, and safety. We conducted a prospective observational cohort study over 1 year on patients undergoing DFPP for various renal indications. There were 15 patients with 39 sessions. The pre- and post-procedure plasma samples of serum IgG, IgA, IgM, fibrinogen, calcium, phosphate, potassium, and magnesium were analyzed. The effluent albumin concentration was also measured, and complications during the hospital stay were recorded. Cumulative removal of serum IgG, IgA, IgM, fibrinogen, and albumin at the end of four sessions were 72%, 89%, 96%, 88.5%, and 21.3%, respectively and effluent albumin concentration was 1.75 - 2.0 times (range: 6.3 g/dl - 7.2 g/dl; mean ± standard deviation (SD) - 7 g/dl ± 0.3 g/dl) the preprocedural serum albumin (mean ± SD - 3.5 g/dl ± 0.5 g/dl). Removal of other plasma components were not statistically significant. Hypotensive episodes were observed only 16.6%, with the usage of effluent concentration albumin as replacement fluid despite an average 2.4 (mean ± SD - 2.4 ± 0.4 l) liters of plasma volume processing each session. DFPP removes IgG, IgA, IgM, fibrinogen, and albumin. The cumulative removal IgG (72%) is suboptimal, whereas IgA (89%) and IgM (96%) are comparable to historical controls. We observed lesser episodes (12.5%) of hypotension with effluent albumin concentration as replacement fluid, and all bleeding complications were observed when serum fibrinogen level was <50 mg/dl.

A Highly Selective Chemosensor for Cyanide Derived from a Formyl-Functionalized Phosphorescent Iridium(III) Complex.

A new phosphorescent iridium(III) complex, bis[2',6'-difluorophenyl-4-formylpyridinato-N,C4']iridium(III) (picolinate) (IrC), was synthesized, fully characterized by various spectroscopic techniques, and utilized for the detection of CN(-) on the basis of the widely known hypothesis of the formation of cyanohydrins. The solid-state structure of the developed IrC was authenticated by single-crystal X-ray diffraction. Notably, the iridium(III) complex exhibits intense red phosphorescence in the solid state at 298 K (ΦPL = 0.16) and faint emission in acetonitrile solution (ΦPL = 0.02). The cyanide anion binding properties with IrC in pure and aqueous acetonitrile solutions were systematically investigated using two different channels: i.e., by means of UV-vis absorption and photoluminescence. The addition of 2.0 equiv of cyanide to a solution of the iridium(III) complex in acetonitrile (c = 20 µM) visibly changes the color from orange to yellow. On the other hand, the PL intensity of IrC at 480 nm was dramatically enhanced ∼5.36 × 10(2)-fold within 100 s along with a strong signature of a blue shift of the emission by ∼155 nm with a detection limit of 2.16 × 10(-8) M. The cyanohydrin formation mechanism is further supported by results of a (1)H NMR titration of IrC with CN(-). As an integral part of this work, phosphorescent test strips have been constructed by impregnating Whatman filter paper with IrC for the trace detection of CN(-) in the contact mode, exhibiting a detection limit at the nanogram level (∼265 ng/mL). Finally, density functional theory (DFT) and time-dependent density functional theory (TD-DFT) calculations were performed to understand the electronic structure and the corresponding transitions involved in the designed phosphorescent iridium(III) complex probe and its cyanide adduct.

Adefovir nephrotoxicity in a renal allograft recipient.

Adefovir dipivoxil, an oral prodrug of adefovir, is used in the treatment of lamivudine-resistant hepatitis B virus (HBV) infection. Nephrotoxicity manifesting as proximal renal tubular dysfunction and acute tubular necrosis (ATN) were commonly reported in the past, when higher doses were used for the treatment of human immunodeficiency virus infection. However, nephrotoxicity is rare at lower doses that are currently recommended for the treatment of HBV infection. A 31-year-old female was detected to be hepatitis B surface antigen positive months after a kidney transplant. The patient was initiated on lamivudine, but developed resistance after 1 year of treatment, at which time low-dose adefovir was added. The patient developed renal allograft dysfunction after 10 months of starting adefovir. Serum creatinine increased from 1.1 mg/dl to 1.9 mg/dl, along with progressively increasing sub-nephrotic proteinuria. Renal allograft biopsy revealed features of ATN. After discontinuation of adefovir, proteinuria resolved and renal dysfunction improved slowly over the next 2 years. Adefovir-induced nephrotoxicity, although uncommon at lower doses, needs to be considered in the differential diagnosis of renal dysfunction and sub-nephrotic proteinuria occurring in patients receiving adefovir for prolonged periods.

Collapsing glomerulopathy following anabolic steroid use in a 16-year-old boy with IgA nephropathy.

Collapsing glomerulopathy (CG) is a proliferative podocytopathy, increasingly recognized in a variety of disease conditions. We report a case of CG in a 16-year-old boy with IgA nephropathy (IgAN) who presented with acute kidney injury, marked proteinuria and hypertension following a short period of anabolic steroid use. Although CG has been associated with long-term anabolic steroid use among body builders, there is no data on the effect of anabolic steroid use in persons with underlying renal disease like IgAN. We postulate that development of CG in our patient could be temporally linked to intake of body-building steroids along with a predisposing background renal disease of IgAN.

Immunoglobulin G4-related tubulointerstitial nephritis associated with interstitial pulmonary disease: Report of a case with review of literature.

Immunoglobulin G4-related disease (IgG4-RD) is an emerging clinicopathological entity. Renal involvement is dominated by tubulointerstitial nephritis (TIN) with IgG4-positive plasma cells and fibrosis. IgG4-RD commonly affects middle-aged to elderly men with accompanying extra-renal lesions such as sialadenitis, lymphadenopathy, or type 1 autoimmune pancreatitis, all of which respond favorably to corticosteroid therapy. The disease burden of IgG4-related kidney disease (IgG4-RKD) in India remains largely underestimated. We report a case of IgG4-RKD manifesting as TIN associated with interstitial pulmonary disease, illustrating typical clinico-pathologic, serologic, immuno-histochemical, and ultrastructural features of this condition. In view of potential amelioration of renal dysfunction with appropriate therapy, the need for awareness of this condition and early diagnosis is highlighted.

Prospective blood pressure measurement in renal transplant recipients.

Blood pressure (BP) control at home is difficult when managed only with office blood pressure monitoring (OBPM). In this prospective study, the reliability of BP measurements in renal transplant patients with OBPM and home blood pressure monitoring (HBPM) was compared with ambulatory blood pressure monitoring (ABPM) as the gold standard. Adult patients who had living-related renal transplantation from March 2007 to February 2008 had BP measured by two methods; OBPM and ABPM at pretransplantation, 2(nd), 4(th), 6(th), and 9(th) months and all the three methods: OBPM, ABPM, and HBPM at 6 months after transplantation. A total of 49 patients, age 35 ± 11 years, on prednisolone, tacrolimus, and mycophenolate were evaluated. A total of 39 were males (79.6%). Systolic BP (SBP) and diastolic BP (DBP) measured by OBPM were higher than HBPM when compared with ABPM. When assessed using OBPM and awake ABPM, both SBP and DBP were significantly overestimated by OBPM with mean difference of 3-12 mm Hg by office SBP and 6-8 mm Hg for office DBP. When HBPM was compared with mean ABPM at 6 months both the SBP and DBP were overestimated by and 7 mm Hg respectively. At 6 months post transplantation, when compared with ABPM, OBPM was more specific than HBPM in diagnosing hypertension (98% specificity, Kappa: 0.88 vs. 89% specificity, Kappa: 0.71). HBPM was superior to OBPM in identifying patients achieving goal BP (89% specificity, Kappa: 0.71 vs. 50% specificity Kappa: 0.54). In the absence of a gold standard for comparison the latent class model analysis still showed that ABPM was the best tool for diagnosing hypertension and monitoring patients reaching targeted control. OBPM remains an important tool for the diagnosis and management of hypertension in renal transplant recipients. HBPM and ABPM could be used to achieve BP control.

Diagnosis and management of Pompe disease.

Pompe disease (PD) is an autosomal-recessively inherited neuromuscular disease that, if not diagnosed and treated early, can be fatal. It can present from early infancy into adulthood. Due to the lack of acid alpha-glucosidase, there is progressive intracellular accumulation of glycogen. The severity of the disease is determined by age of onset, organ involvement including the degree of severity of muscle involvement, as well as rate of progression. PD is classified into two groups: infantile and late-onset, each having two subgroups. The need for two tests performed by separate methods (screening and confirmatory) is outlined. It is imperative to try to reduce the time to diagnosis and to recognise the possibilities of false-positive results. A multidisciplinary team approach to treatment of affected patients is optimum with, as team leader, a physician who has experience in managing this rare disorder. In this article, we present a brief overview of the disease and provide guidelines for diagnosis and management of this condition in South Africa.

Profile of incident chronic kidney disease related-mineral bone disorders in chronic kidney disease Stage 4 and 5: A hospital based cross-sectional survey.

Chronic kidney disease related-mineral bone disorder (CKD-MBD) has been poorly studied in pre-dialysis Indian CKD patients. We aimed to study the clinical, biochemical and extra skeletal manifestations of untreated CKD-MBD in pre-dialysis Stage 4 and 5 CKD patients attending nephrology out-patient clinic at a tertiary care hospital in South India. A hospital based cross-sectional survey including, demographic profile, history of CKD-MBD symptoms, measurement of serum calcium, phosphate, parathyroid hormone, 25 hydroxy vitamin D (25(OH) D) and alkaline phosphatase; lateral abdominal X-rays for abdominal aortic calcification (AAC) and echocardiography for valvular calcification (VC) was carried out. Of the 710 patients surveyed, 45% had no CKD-MBD related symptom. Prevalence of hypocalcemia, hyperphosphatemia, hyperparathyroidism (>150 pg/mL) and 25(OH) D levels <30 ng/mL was 66.3%, 59%, 89.3% and 74.7% respectively. Echocardiography was carried out in 471 patients; 96% of whom had VC (calcification score ≥1). Patients with VC were older and had lower 25(OH) D levels than those without. Lateral abdominal X-rays were obtained in 558 patients, 6.8% of whom were found to have AAC, which was associated with older age. Indian patients with incident CKD-MBD have a high prevalence of hypocalcemia, 25(OH) D deficiency and VC even prior to initiating dialysis while AAC does not appear to be common. The association between 25(OH) D deficiency and VC needs further exploration.

Significance of pre-transplant anti-HLA antibodies detected on an ELISA mixed antigen tray platform.

This study aims at examining the clinical impact, of antibodies detected on an ELISA mixed antigen tray format (LATM, One Lambda) in the absence of complement dependent cytotoxicity (CDC) positivity. All patients who underwent renal transplantation in 2007 and 2008 had their final pre-transplant sera retrospectively analyzed by the LATM assay. These patients were then followed-up with clinical, biochemical, and histopathological end points defined by elevation of serum creatinine and/or histopathological criteria. Among 164 patients who were studied, 149 received grafts from live related donors and 15, from deceased donors. 31 (19%) of the transplanted patients demonstrated pre-transplant anti-HLA IgG antibodies on the assay. Totally, 15 were positive for class I antibodies, 4 for class II antibodies, and 12 for both class I and class II antibodies. 44 patients (36%) experienced rejection. 8 out of 31 (26%) ELISA positive patients and 36 out of 133 (27%) ELISA negative patients experienced rejection. Among 15 patients who received deceased donor transplants, 4 were positive for ELISA, and 11 were negative. All 4 (100%) of the ELISA positive patients experienced rejection as compared to 3 out of 11 (27%) ELISA negative patients (P = 0.01). The ELISA LATM assay did not show any predictive value for rejection in our overall patient population; however, results in the specific setting of deceased donor transplants merit further exploration.