Search

Results of three consecutive clinical trials of therapy of anaerobic infections in cancerpatients were compared, using doxycycline versus tinidazole, clindamycin versus cefoxitin and tinidazole versus tinidazole plus amikacin.Mixed aerobic and anaerobic infections had a similar response rate when treatment consisted of a specific anti-anaerobic drug as compared to a broader antimicrobial therapy directed against aerobic and anaerobic pathogens.Even when the anaerobic pathogen was resistant to therapy, many patients were cured. Surgical drainage played an important role, but was difficult to assess precisely. [ABSTRACT FROM PUBLISHER]

The Working Party on Safety in Biotechnology of the European Federation of Biotechnology reported [Künzi M, et al. Safe Biotechnology (1) - General considerations. Appl Microbiol Biotechnol 21:1-6] on the classification of human pathogens and other microorganisms. It is proposed to relate the various risk classes of these organisms to the categories of physical containment for recombinant DNA (rDNA) organisms according to the OECD report [OECD Report (1986) 'Recombinant DNA Safety Considerations', Paris]. In view of the differences in the numbering systems of the EFB for risk classes (1-4) and the OECD system of Good Industrial Large Scale Practice (GILSP) and containment categories 1-3, the former have been given alternative names. Relationships of the EFB-Classification of Microorganisms according to risk and OECD safety precautions have been defined (Table 1). [ABSTRACT FROM AUTHOR]

Teicoplanin (0.2 g) or vancomycin (1 g) were infused over 3 and 50 min respectively to six male volunteers in a cross-over study. Each drug was administered twice at a 14 h interval. The pharmacokinetics of both drugs were accurately described using a two-compartment model. Vancomycin had a shorter half-life (5.8±1.8 h) compared to teicoplainin (33.2±5.1h; <0.001) One hour serum was tested for serum bactericidal activity against ten strains each of (median serum bactericidal activity 1:16 for teicoplanin; 1:32 for vancomycin), (1:32 for teicoplanin and for vancomycin) and Streptococcus faecalis (1: 2 for both drugs). Serum killing rate studies showed a slower rate of killing of with teicoplanin (<1 log cfu/ml over 6 h) than with vancomycin (4 log cfu/ml over 6 h). [ABSTRACT FROM PUBLISHER]

Timentin (ticarcillin plus clavulanic acid) plus amikacin was administered as an empirical regimen to 52 febrile granulocytopenic patients with cancer and appeared as effective as the other commonly recommended combinations of antimicrobial agents. A favourable response was observed in 61% of episodes with bacteraemia and in 83% of the episodes without bacteraemia. However, the efficacy in Grampositive bacteraemia was suboptimal and the emergence of superinfections caused by Gram-positive cocci may represent a clinical challenge. [ABSTRACT FROM PUBLISHER]

Ten volunteers received three doses of 500 mg ciprofloxacin, orally every 12 hours. After the last dose, mean serum levels were (mg/l +/- SD) 2.4 +/- 0.83 at 1 h; 0.91 +/- 0.30 at 4 h and 0.18 +/- 0.04 at 12 h. At 1 h the median serum bactericidal activity was satisfactory only against the Escherichia coli (1:256) and Klebsiella pneumoniae (1:128). In urine collected from 0 to 4 h and 8 to 12 h after the last dose, the mean ciprofloxacin level was respectively 482.5 +/- 324.7 and 80.9 +/- 48.2 mg/l +/- SD. Bactericidal activity in urine was high even against the least susceptible species tested: Pseudomonas aeruginosa, Staphylococcus aureus and Streptococcus faecalis. A post antibiotic effect was demonstrated in 22 out of the 29 strains tested, ranging mainly from 1 to 3 h. Ciprofloxacin 500 mg orally twice a day is a bactericidal regimen against a wide range of urinary pathogens but has a limited systemic activity. [ABSTRACT FROM AUTHOR]

Azlocillin (5 g), ticarcillin (5 g) and ticarcillin (5 g) plus clavulanic acid (200 mg) were administered intravenously on separate days to human volunteers. Serum levels 1 h after the infusion were (mean +/- S.E.): 263 +/- 40 mg/1 for azlocillin, 238 +/- 56 mg/l for ticarcillin and 5.5 +/- 1.9 mg/l for clavulanic acid. Serum withdrawn at 0.5 h was titrated against ten strains of Staphylococcus aureus, ten Klebsiella pneumoniae and nine Pseudomonas aeruginosa of which four were resistant to ticarcillin. Against Staph. aureus and K. pneumoniae, median serum bactericidal activity (SBA) and percentage of sera with SBA greater than or equal to 1:8 were greater with ticarcillin plus clavulanic acid (median SBA 1:32 and 85% of sera with SBA greater than or equal to 1:8) than with the other two regimens. There were no differences in activity against Ps. aeruginosa. [ABSTRACT FROM AUTHOR]

Serum bactericidal activity (SBA) greater than or equal to 1:8 correlates with the clinical effectiveness of antibiotics. Ten healthy young volunteers received iv on separate days cefoperazone 1, 2, or 3 g and ceftazidime 1, 2, or 3 g. The serum levels 1 and 6 h after the administration of cefoperazone 1, 2 and 3 g were respectively 52 and 7 mg/l, 122 and 13 mg/l, 190 and 22 mg/l. The serum levels of ceftazidime 1, 2 and 3 g, after 1 h and 6 h were 28 and 8, 56 and 9, 78 and 13 mg/l. The SBA was determined against seven strains of Pseudomonas aeruginosa with MBC of 1.6-12.5 mg/l of cefoperazone and 0.8-6.2 mg/l of ceftazidime. Increased dosage of cefoperazone and ceftazidime led to a significant increase in the SBA's greater than or equal to 1:8 at 1 h (P less than 0.01). In sera obtained 1 h and 6 h after the injection of the antibiotics, 97% and 51% of the strains were inhibited by ceftazidime 2 g, while 1 g was inhibitory on 84% (1 h) and 8% (6 h) of the strains. Ceftazidime 1 g produced SBA's greater than or equal to 1:8 significantly more often than did cefoperazone 3 g (P less than 0.01) at 1 h. The rate of killing with all ceftazidime regimens was similar and slightly higher than that of any cefoperazone regimen. Ceftazidime seems more effective than cefoperazone against Ps. aeruginosa; however, increased MBC values were observed during killing curves studies with both drugs. [ABSTRACT FROM AUTHOR]

Cefoperazone, a new broad-spectrum cephalosporin, was administered by continuous infusion or intermittent injection to 20 and 25 patients respectively with gram-negative bacillary septicemia most of whom had severe underlying disease. No difference was observed in the clinical response of the two groups. The overall rate of favourable response was 76 %. Of the 40 non-neutropenic patients treated three died of infection despite sensitivity of the organism, three improved temporarily and three died as the result of superinfection. Three of the five neutropenic patients treated failed to respond to cefoperazone therapy, despite adequate serum bactericidal activity. Tolerance to cefoperazone was satisfactory. Emergence of cefoperazone-resistant strains leading to relapse or superinfection was not a major cause of failure. [ABSTRACT FROM AUTHOR]

Background: Chronic wounds are a fundamental issue for patients with epidermolysis bullosa (EB). Herein, we assess the natural history of wound closure in patients with EB who were randomly assigned to the vehicle-control arm of the multicenter, randomized, double-blind, phase 3 ESSENCE (NCT02384460) trial., Methods: ESSENCE was designed to assess the efficacy and safety of a topical cream formulation of 6% allantoin (SD-101 6%) vs vehicle (SD-101 0%) in patients ≥1 month old who had a diagnosis of EB (simplex, recessive dystrophic, or intermediate junctional) and a target wound 10-50 cm 2 present for ≥21 days. Time to complete target wound closure and the proportion of patients with target wound closure over time were analyzed overall and by parameters including patient age and baseline body surface area index (BSAi) of total wound burden (< 5% and ≥ 5%). Changes in BSAi of lesional skin, pain, and itching were also assessed., Results: The vehicle-control arm included 87 patients. Mean (standard deviation [SD]) time to target wound closure within 3 months was 53.6 (28.6) days, with a range of 14 to 142 days. The proportion of patients with target wound closure increased over time from 7.1% at day 14 to 53.6% at month 3. Mean (SD) changes from baseline in BSAi of total wound burden and BSAi of lesional skin at month 3 were -2.3% (6.3) and -5.0% (13.5) of total body coverage, respectively. Reductions in pain and itching were observed at day 7 and maintained for 3 months. Faster healing times and a greater proportion of patients with wound closure were observed in patients aged 1 month to < 2 years; those with wounds < 30 days old, and in those with BSAi of total body wound burden < 5%., Conclusions: Treatment response observed in the vehicle-control arm of the ESSENCE study was unexpectedly high and may have been due to unforeseen benefits of vehicle or enhanced wound care provided by the clinical trial staff. These observations will help inform the study design of future trials in patients with EB., Trial Registration: ClinicalTrials.gov , NCT02384460 ; Date of registration: February 13, 2015; First participant enrollment: March 11, 2015.

Background: Epidermolysis bullosa (EB) is a rare genetic disorder that manifests as blistering and/or skin erosion. There is no approved treatment for EB; current standard of care consists of wound and pain management. SD-101 6% is a topical cream containing 6% allantoin that was developed for treating skin lesions in patients with EB. The aim of this phase 3, multicenter, randomized, double-blind, vehicle-controlled study was to assess the efficacy and safety of SD-101 6% cream versus vehicle (0% allantoin) on lesions in patients with EB., Methods: Eligible patients were ≥1 month old, had a diagnosis of EB (simplex, recessive dystrophic, or intermediate junctional) and a target wound 10-50 cm 2 in size that was present for ≥21 days. Patients were randomly assigned to SD-101 6% cream or vehicle, which was applied topically once a day to the entire body for 3 months. Primary efficacy endpoints were time to complete target wound closure within 3 months and the proportion of patients who experienced complete target wound closure within 3 months. Post hoc subgroup analyses were conducted by patient age and in those with body surface area index of total body wound burden ≥5% at baseline., Results: In total, 169 patients were enrolled and randomly assigned to SD-101 6% (n = 82) or vehicle (n = 87). Baseline demographics and disease characteristics were similar between treatment groups. There were no statistically significant differences between treatment groups in time to target wound closure (hazard ratio, 1.004; 95% confidence interval [CI] 0.651, 1.549; P = 0.985) or proportion of patients with complete target wound closure within 3 months (odds ratio [95% CI], 0.733 [0.365, 1.474]; nominal P = 0.390). A positive trend toward faster wound closure with SD-101 6% versus vehicle was observed in patients aged 2 to <12 years and those with total body wound burden ≥5% at baseline. SD-101 6% cream was well tolerated., Conclusions: SD-101 6% cream for treatment of EB-associated lesions was not more effective than vehicle in shortening the time to complete target wound closure or achieving complete target wound closure within 3 months., Trial Registration: ClinicalTrials.gov, NCT02384460; Date of trial registration, February 13, 2015; First participant enrolled, March 11, 2015.

Background: Fabry disease is a progressive X-linked lysosomal disorder. In this subgroup analysis of the global phase III ATTRACT study, the efficacy and safety of oral migalastat, a pharmacologic chaperone, were investigated in Japanese patients with Fabry disease., Methods: Patients were randomly assigned to receive migalastat (150 mg every other day) or to continue biweekly enzyme replacement therapy infusions (ERT; agalsidase alfa 0.2 mg/kg or agalsidase beta 1.0 mg/kg) for 18 months followed by a 12-month open-label extension during which all patients received migalastat. End points included glomerular filtration rate (estimated and measured), left ventricular mass index (LVMi), composite clinical outcomes, leukocyte alpha-galactosidase A activity, plasma globotriaosylsphingosine (lyso-Gb 3 ), and safety., Results: Data from 7 Japanese patients (migalastat, 5; ERT, 2), mean age 55 years, with high disease burden, were analyzed. All patients in the migalastat group completed the open-label comparison and extension periods. At 18 months, efficacy in the Japanese patient population was similar to that in the overall ATTRACT population. Migalastat treatment increased leukocyte alpha-galactosidase A activity, stabilized renal function, and decreased LVMi. Plasma lyso-Gb 3 levels remained low and stable. Additionally, the long-term extension study showed that efficacy of migalastat was maintained for up to 48 months. Migalastat was safe and well tolerated in the Japanese patients, as in the overall ATTRACT population., Conclusion: Migalastat can be used to treat Japanese patients with Fabry disease with GLA mutations amenable to migalastat according to the dosage and administration approved in other countries., Trial Registration Numbers: ClinicalTrials.gov, NCT01218659 and NCT02194985.

Background: Little information is available regarding the burden of living with and managing epidermolysis bullosa, including the distinct challenges faced by patients with different disease types/subtypes., Methods: A 90-question/item survey was developed to collect demographics, diagnostic data, management practices, and burden of illness information for patients with epidermolysis bullosa living in the United States. Recruitment was conducted via email and social media in partnership with epidermolysis bullosa patient advocacy organizations in the United States, and the survey was conducted via telephone interview by a third-party health research firm. Respondents aged ≥ 18 years with a confirmed diagnosis of epidermolysis bullosa or caring for a patient with a confirmed diagnosis of epidermolysis bullosa were eligible to participate in the survey., Results: In total, 156 responses were received from patients (n = 63) and caregivers (n = 93) representing the epidermolysis bullosa types of simplex, junctional, and dystrophic (subtypes: dominant and recessive). A large proportion of patients (21%) and caregivers (32%) reported that the condition was severe or very severe, and 19% of patients and 26% of caregivers reported a visit to an emergency department in the 12 months prior to the survey. Among the types/subtypes represented, recessive dystrophic epidermolysis bullosa results in the greatest wound burden, with approximately 60% of patients and caregivers reporting wounds covering > 30% of total body area. Wound care is time consuming and commonly requires significant caregiver assistance. Therapeutic options are urgently needed and reducing the number and severity of wounds was generally ranked as the most important treatment factor., Conclusions: Survey responses demonstrate that epidermolysis bullosa places a considerable burden on patients, their caregivers, and their families. The limitations caused by epidermolysis bullosa mean that both patients and caregivers must make difficult choices and compromises regarding education, career, and home life. Finally, survey results indicate that epidermolysis bullosa negatively impacts quality of life and causes financial burden to patients and their families.

In hypoparathyroidism, inappropriately low levels of parathyroid hormone lead to unbalanced mineral homeostasis. The objective of this study was to determine the effect of recombinant human parathyroid hormone, rhPTH(1-84), on phosphate and vitamin D metabolite levels in patients with hypoparathyroidism. Following pretreatment optimization of calcium and vitamin D doses, 124 patients in a phase III, 24-week, randomized, double-blind, placebo-controlled study of adults with hypoparathyroidism received subcutaneous injections of placebo or rhPTH(1-84) (50 µg/day, titrated to 75 and then 100 µg/day, to permit reductions in oral calcium and active vitamin D doses while maintaining serum calcium within 2.0-2.2 mmol/L). Predefined endpoints related to phosphate homeostasis and vitamin D metabolism were analyzed. Serum phosphate levels decreased rapidly from the upper normal range and remained lower with rhPTH(1-84) (P < 0.001 vs. placebo). At week 24, serum calcium-phosphate product was lower with rhPTH(1-84) vs. placebo (P < 0.001). rhPTH(1-84) treatment resulted in significant reductions in oral calcium dose compared with placebo (P < 0.001) while maintaining serum calcium. After pretreatment optimization, baseline serum 25-hydroxyvitamin D (25[OH]D) and 1,25-dihydroxyvitamin D (1,25[OH] 2 D) levels were within the normal range in both groups. After 24 weeks, 1,25(OH) 2 D levels were unchanged in both treatment groups, despite significantly greater reductions in active vitamin D dose in the rhPTH(1-84) group. In hypoparathyroidism, rhPTH(1-84) reduces serum phosphate levels, improves calcium-phosphate product, and maintains 1,25(OH) 2 D and serum calcium in the normal range while allowing significant reductions in active vitamin D and oral calcium doses., Competing Interests: BLC, JPB, and DMS have received institutional research grants from and served as advisory group members for NPS Pharmaceuticals, Inc.; MM and TJV have served as advisory group members for NPS Pharmaceuticals, Inc.; HL was an employee of NPS Pharmaceuticals, Inc., at the time the study was conducted and the manuscript was written. Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Informed consent Informed consent was obtained from all individual participants included in the study.

Objective: Hypoparathyroidism is characterized by inadequate parathyroid hormone (PTH), resulting in hypocalcemia, hyperphosphatemia, and bone abnormalities. Adults with hypoparathyroidism treated with recombinant human PTH, rhPTH(1-84), in the 24-week, phase III REPLACE study maintained serum calcium despite reductions in oral calcium and active vitamin D. This study assessed the long-term efficacy and safety of rhPTH(1-84) for hypoparathyroidism., Methods: This was a 24-week, open-label, flexible-dose extension study of REPLACE (REPEAT) conducted in 3 outpatient centers in Hungary. Patients who previously completed or enrolled in REPLACE received 50 μg/day rhPTH(1-84), escalated to 75 and then to 100 μg/day, if needed, to reduce active vitamin D and oral calcium. The primary endpoint was ≥50% reduction in oral calcium (or ≤500 mg/day) and active vitamin D (or calcitriol ≤0.25 μg/day or alfacalcidol ≤0.50 μg/day) with normocalcemia., Results: Twenty-four patients (n = 16 previously treated with rhPTH[1-84]; n = 8 rhPTH[1-84]-naïve) were enrolled and completed the study. At Week 24, 75% of patients (95% confidence interval [CI], 53.3-90.2%) achieved the study endpoint; 58% eliminated oral calcium and active vitamin D. Urinary calcium, serum phosphate, and calcium × phosphate (Ca × P) product decreased by Week 24. Mean serum bone turnover markers increased with rhPTH(1-84). Treatment-emergent adverse events (TEAEs) were reported by 92% of patients. No serious adverse events (AEs) occurred., Conclusion: This study used a simplified treatment algorithm intended to better mimic typical clinical practice and demonstrated the extended efficacy and safety of rhPTH(1-84) in patients with hypoparathyroidism and confirmed the REPLACE findings. Sustained rhPTH(1-84) efficacy up to 48 weeks was observed despite treatment interruption between studies.

Objective: Hypoparathyroidism is a rare disease caused by lack of parathyroid hormone (PTH) leading to hypocalcemia, hyperphosphatemia, and a variety of symptoms. This study aimed to quantify the clinical and social burden of illness from the perspective of affected patients., Methods: A web-based instrument was developed with input from patients, clinical experts, and the Hypoparathyroidism Association. Qualifying participants were ≥18 years old, diagnosed with hypoparathyroidism for ≥6 months, and U.S. residents. Questions focused on demographics, diagnosis perceptions, current attitudes, medical management, current symptoms, acute episodes, comorbidities, personal life, and employment., Results: A total of 374 adults (mean age, 49 ± 12 years; female, 85%) with hypoparathyroidism (mean duration, 13 ± 12 years; severe condition, 30.5%) completed the survey. Patients reported visiting a mean of 6 ± 8 physicians before and after their diagnosis. The majority strongly agreed with feeling unprepared to manage the condition at diagnosis (56%), that controlling their hypoparathyroidism is harder than expected (60%), and that they were concerned about long-term complications of their current medications (75%). More than 10 symptoms were experienced by 72% of patients in the preceding 12 months, despite current management regimens. Symptoms were experienced for a mean of 13 ± 9 hours/day. Hospital stays or emergency department visits were required by 79% of patients. 45% reported significant interference with their lives, 85% reported an inability to perform household activities, and 20% experienced a disease-associated change in employment status., Conclusion: Patients with hypoparathyroidism have a high burden of illness and experience a broad spectrum of symptoms, with a multidimensional impact on their lives.

Background: Impaired mineral homeostasis affecting calcium, phosphate, and magnesium is a result of parathyroid hormone (PTH) deficiency in hypoparathyroidism. The current standard of treatment with active vitamin D and oral calcium does not control levels of these major minerals. Recombinant full-length human PTH 1-84 (rhPTH[1-84]) is being developed for the treatment of hypoparathyroidism., Objective: The goal of this study was to investigate the pharmacokinetics and pharmacodynamics of a single subcutaneous injection of rhPTH(1-84) in patients with hypoparathyroidism., Methods: This was an open-label, dose-escalating study of single subcutaneous administration of 50 µg and then 100 µg of rhPTH(1-84). Enrolled patients (age range, 25-85 years) had ≥12 months of diagnosed hypoparathyroidism defined according to biochemical evidence of hypocalcemia with concomitant low-serum intact PTH and were taking doses ≥1000 mg/d of oral calcium and ≥0.25 µg/d of active vitamin D (oral calcitriol). The patient's prescribed dose of calcitriol was taken the day preceding but not on the day of or during the 24 hours after rhPTH(1-84) administration. Each patient received a single 50-µg rhPTH(1-84) dose, had at least a 7-day washout interval, and then received a single 100-µg rhPTH(1-84) dose. The following parameters were assessed: plasma PTH; serum and urine total calcium, magnesium, phosphate, and creatinine; and urine cyclic adenosine monophosphate., Results: After administration of rhPTH(1-84) 50 µg (n = 6) and 100 µg (n = 7), the approximate t½ was 2.5 to 3 hours. Plasma PTH levels increased rapidly, then declined gradually back to predose levels at ~12 hours. The median AUC was similar with calcitriol and rhPTH(1-84) for serum 1,25-dihydroxyvitamin D (calcitriol, 123-227 pg · h/mL; rhPTH[1-84], 101-276 pg · h/mL), calcium (calcitriol, 3.3-3.7 mg · h/dL; rhPTH[1-84], 3.3-7.6 mg · h/dL), and magnesium (calcitriol, 0.7-0.9 mg · h/dL; rhPTH[1-84], 1.3-2.8 mg · h/dL). In contrast, the median AUC for phosphate was strongly negative with rhPTH(1-84) (calcitriol, -1.0 to 0.8 mg · h/dL; rhPTH[1-84], -21.3 to -26.5 mg · h/dL). Compared with calcitriol, rhPTH(1-84) 50 µg reduced 24-hour calcium excretion and calcium-to-creatinine ratios by 12% and 23%, respectively, and rhPTH(1-84) 100 µg reduced them by 26% and 27%. There was little overall impact on urine magnesium levels. Compared with calcitriol, rhPTH(1-84) 50 µg increased urinary phosphate excretion and phosphate-to-creatinine ratios by 53% and 54%, respectively, and rhPTH(1-84) 100 µg increased them by 45% and 42%. Urine cyclic adenosine monophosphate-to-creatinine ratio increased with rhPTH(1-84) by 2.3-fold (50 µg) and 4.4-fold (100 µg) compared with calcitriol., Conclusions: PTH replacement therapy with rhPTH(1-84) regulated mineral homeostasis of calcium, magnesium, phosphate, and vitamin D metabolism toward normal in these study patients with hypoparathyroidism., (Copyright © 2014 The Authors. Published by EM Inc USA.. All rights reserved.)

Background: Hypoparathyroidism results in impaired mineral homoeostasis, including hypocalcaemia and hyperphosphataemia. Treatment with high-dose oral calcium and active vitamin D does not provide adequate or consistent control of biochemical indices and can lead to serious long-term complications. We aimed to test the efficacy, safety, and tolerability of once-daily recombinant human parathyroid hormone 1-84 (rhPTH[1-84]) in adults with hypoparathyroidism., Methods: In this double-blind, placebo-controlled, randomised phase 3 study (REPLACE), we recruited patients with hypoparathyroidism (≥ 18 months duration) aged 18-85 years from 33 sites in eight countries. After an optimisation period, during which calcium and active vitamin D doses were adjusted to achieve consistent albumin-corrected serum calcium, patients were randomly assigned (2:1) via an interactive voice response system to 50 μg per day of rhPTH(1-84) or placebo for 24 weeks. Active vitamin D and calcium were progressively reduced, while rhPTH(1-84) could be titrated up from 50 μg to 75 μg and then 100 μg (weeks 0-5). The primary endpoint was the proportion of patients at week 24 who achieved a 50% or greater reduction from baseline in their daily dose of oral calcium and active vitamin D while maintaining a serum calcium concentration greater than or the same as baseline concentrations and less than or equal to the upper limit of normal, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00732615., Findings: Between June 23, 2009, and Feb 28, 2011, 134 eligible patients were recruited and randomly assigned to rhPTH(1-84) (n=90) or placebo (n=44). Six patients in the rhPTH(1-84) group and seven in the placebo group discontinued before study end. 48 (53%) patients in the rhPTH(1-84) group achieved the primary endpoint compared with one (2%) patient in the placebo group (percentage difference 51.1%, 95% CI 39.9-62.3; p<0.0001). The proportions of patients who had at least one adverse event were similar between groups (84 [93%] patients in the rhPTH[1-84] group vs 44 [100%] patients in the placebo group), with hypocalcaemia, muscle spasm, paraesthesias, headache, and nausea being the most common adverse events. The proportions of patients with serious adverse events were also similar between the rhPTH(1-84) group (ten [11%] patients) and the placebo group (four [9%] patients)., Interpretation: 50 μg, 75 μg, or 100 μg per day of rhPTH(1-84), administered subcutaneously in the outpatient setting, is efficacious and well tolerated as a PTH replacement therapy for patients with hypoparathyroidism., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Hypoparathyroidism is a rare endocrine disorder whose incidence and prevalence have not been well defined. This study aimed to 1) estimate the number of insured adult patients with hypoparathyroidism in the United States and 2) obtain physician assessment of disease severity and chronicity. Prevalence was estimated through calculation of diagnoses of hypoparathyroidism in a large proprietary health plan claims database over a 12-month period from October 2007 through September 2008 and projected to the US insured population. Incidence was also calculated from the same database by determining the proportion of total neck surgeries resulting in either transient (≤6 months) or chronic (>6 months) hypoparathyroidism. A physician primary market research study was conducted to assess disease severity and determine the percentage of new nonsurgical patients with hypoparathyroidism. Incidence data were entered into an epidemiologic model to derive an estimate of prevalence. The diagnosis-based prevalence approach estimated 58,793 insured patients with chronic hypoparathyroidism in the United States. The surgical-based incidence approach yielded 117,342 relevant surgeries resulting in 8901 cases over 12 months. Overall, 7.6% of surgeries resulted in hypoparathyroidism (75% transient, 25% chronic). The prevalence of chronic hypoparathyroidism among insured patients included in the surgical database was estimated to be 58,625. The physician survey found that 75% of cases treated over the past 12 months were reported due to surgery and, among all thyroidectomies and parathyroidectomies and neck dissections performed in a year, 26% resulted in transient hypoparathyroidism and 5% progressed to a chronic state. In conclusion, the two claims-based methods yielded similar estimates of the number of insured patients with chronic hypoparathyroidism in the United States (~58,700). The physician survey was consistent with those calculations and confirmed the burden imposed by hypoparathyroidism., (© 2013 American Society for Bone and Mineral Research.)