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BMC Veterinary Research
Retrospective evaluation of toceranib phosphate (Palladia®) use in the treatment of inoperable, metastatic, or recurrent canine pheochromocytomas: 5 dogs (2014–2017)
Margaret L. Musser ORCID: orcid.org/0000-0003-4350-06141,2,
Kathryn L. Taikowski1,3,
Chad M. Johannes2 &
Philip J. Bergman4
BMC Veterinary Research volume 14, Article number: 272 (2018) Cite this article
Effective treatment options for inoperable, metastatic, or recurrent canine pheochromocytomas are lacking. In humans, specific germline mutations exist that drive the development of pheochromocytomas. Pharmaceutical blockade of these abnormalities with small molecule inhibitors are an effective treatment strategy. Similar mutations may exist in the dog, and thus, treatment with similar small molecule inhibitors may provide a survival advantage. The purpose of this study was to assess the role of toceranib phosphate in the treatment of inoperable, metastatic, or recurrent canine pheochromocytomas.
Retrospectively, medical records of dogs that had a diagnosis or suspect diagnosis of a pheochromocytoma were reviewed for information regarding response to toceranib phosphate and overall outcome. Five dogs were identified that fit the inclusion criteria. All five experienced clinical benefit (1 partial response, 4 stable disease). Progression-free interval (PFI) for the dog with the partial response was 61 weeks. PFI for the two dogs with stable measurable disease were 36 weeks and 28 weeks. PFI in the two dogs with stable metastatic disease were at least 11 weeks and 18 weeks.
Based on this limited series of dogs, the results suggest that toceranib may have biological activity in dogs with primary and metastatic pheochromocytomas. Larger studies are needed to define the use and response to toceranib in dogs with gross, microscopic, and metastatic pheochromocytoma.
Pheochromocytomas (PCs) are tumors comprised of neoplastic chromaffin cells of the adrenal medulla. Pheochromocytomas overproduce catecholamines, specifically epinephrine and norepinephrine, in an episodic manner, leading to intermittent clinical signs, including weakness, collapse, hypertension, panting, polyuria and polydipsia, and decreased appetite [1, 2]. Pheochromocytomas are uncommon in the dog, but must be considered malignant as severe consequences including invasion into the caudal vena cava, retroperitoneal hemorrhage, and metastatic spread can occur [2, 3].
Definitive treatment of a PC requires adrenalectomy [2]. However, anesthesia and surgical removal of an adrenal tumor is a high-risk procedure, carrying an overall 51% postoperative complication rate, which increases to 60% in dogs with PC [4]. These complications can include significant blood pressure variations, tachyarrhythmias, intraoperative hemorrhage, and intraoperative death [3, 4]. Vascular invasion into the caudal vena cava, reported in up to 82% of cases, [4, 5] complicates the surgical approach, but the impact on survival in these cases is unclear [4,5,6]. A median survival time of 53 weeks has been reported in dogs following surgical removal of a PC [7], with some living for 2–3 years [8, 9]. However, some PCs are not amenable to surgical removal or surgery is contraindicated due to the presence of widespread metastatic disease [6]. The benefit of medical treatment in these cases is unknown.
Pheochromocytomas affect 2 to 8 per million people per year [10, 11] and are biologically similar to those that affect dogs [1]. Standard of care is surgical removal, which often results in a normal lifespan for those individuals with local disease. However, 10–30% will develop distant metastatic disease, and in the 6.5 to 16.5% of patients that develop recurrence after surgical removal [12,13,14], 50% develop distant metastasis [14]. In the case of any distant metastasis, only 40–60% of patients survive an additional 5 years [1, 15]. These advanced-stage malignant PCs are resistant to chemotherapy and radiation therapy, and the side effects of treatment often outweigh the benefits [16].
In humans, hereditary germline mutations, and abnormally regulated angiogenesis and oxygen metabolism pathways, drive the pathogenesis of many metastatic PCs [17]. Therefore, recent PC research and clinical trials have focused on drugs that target these specific abnormalities. Sunitinib malate is a small molecule inhibitor that targets multiple tyrosine kinase receptors, including c-KIT, FLT3 and RET, and those that help to drive angiogenesis including vascular endothelial growth factor receptors (VEGFR) 1 and 2, and platelet-derived growth factor receptor-β (PDGFRβ) [12, 17, 18]. Recent research suggests that use of sunitinib in human patients with advanced PCs will result in tumor size reduction, disease stabilization, and improvement of hypertension [16, 17, 19, 20].
Toceranib phosphate is a tyrosine kinase inhibitor (TKI) available in veterinary medicine that is molecularly similar to sunitinib, and blocks the same key receptors associated with angiogenesis: VEGFR and PDGFR [21, 22]. Thus, it may be a good treatment option for canine patients suffering from advanced PCs that are biologically similar to human PCs, or in those patients where surgical removal is not a viable treatment option. This study aimed to determine if a response to toceranib is present in dogs with advanced inoperable, recurrent, or metastatic PCs. Based on the human literature, we hypothesized that dogs with a measurable PC or metastatic disease would have a biological response to treatment with toceranib.
Medical records of dogs diagnosed with a PC and treated with toceranib were collected and reviewed via solicitation through the American College of Veterinary Internal Medicine Oncology Listserv, an e-mail based forum for oncology diplomates. Only dogs with complete records regarding signalment, history, initial complaint, physical examination findings, abdominal and thoracic imaging, treatment with toceranib for at least 10 weeks, and with adequate follow-up including records of side effects, were included in the study. The diagnosis of a PC was based on histopathology of the surgically removed tumor, or suspicion of a PC based on elevated plasma or urine metanephrine or normetanephrine levels as previously described [3, 23,24,25,26,27].
Data collected included breed, weight, clinical signs at diagnosis and duration of clinical signs, findings of thoracic and abdominal imaging, histopathology results, blood pressure, results of fundic examinations, urine metanephrine/normetanephrine levels if available, evidence of cardiac arrhythmias, therapy prior to the start of toceranib, reason for toceranib use (inoperable measurable disease, microscopic disease, treatment of recurrent disease, metastatic disease, or maintenance after completion of other therapy), toceranib dose and dose schedule, duration of toceranib treatment, best response to treatment using previously defined criteria [28], side effects induced by toceranib using the veterinary cooperative oncology group-defined criteria [29], concurrent chemotherapy and supportive medications, concurrent diseases, and patient outcome.
Progression-free interval (PFI) was calculated for all dogs and defined as the time from the day of first toceranib treatment to the time of disease progression (defined as either local regrowth, local progression, and/or metastasis), to the time of toceranib discontinuation due to adverse effects, or to the time of data submission. For dogs with measurable disease, as in previous publications describing the use of toceranib in dogs, clinical benefit (CB) was determined by best response to therapy and was defined as a complete response (CR) or partial response (PR) of any duration, or stable disease (SD) of at least ten weeks in duration [30].
Response to therapy was evaluated via serial abdominal ultrasounds, thoracic radiographs, and in one case urine catecholamine measurements. Animals experiencing SD less than 10 weeks in duration or progressive disease (PD) as their best response to toceranib were not classified as achieving CB.
Data for 6 dogs from 5 different sites were received. Five dogs were identified that fit the inclusion criteria (Table 1).
Table 1 Summary of patient characteristics and response to toceranib
The sixth dog did not have adequate evidence of a PC diagnosis, and so was excluded from analysis. There were four spayed females and one castrated male. Breeds included one of each: Shih Tzu, Australian Terrier, Pomeranian, Dachshund, and Pit Bull. Mean weight was 12.1 kg (range 2.6–29 kg) with a mean age of 11.5 years (range 9.5–14 years). Clinical signs at diagnosis were varied, but included prolonged gastrointestinal signs (vomiting, diarrhea, decreased appetite, and weight loss) in three dogs, and exercise intolerance, heavy panting, and polyuria/polydipsia in two dogs. One dog was non-clinical and the PC was an incidental finding during work-up of a concurrent disease. Excluding this dog, clinical signs for the other four dogs were present for a mean of 22 weeks (range 1–52 weeks).
Physical examinations were unremarkable in all dogs. No cardiac arrhythmias were noted in any dogs at any time. A fundic examination was performed in four dogs, which was normal in all patients evaluated.
Abdominal radiographs were taken in one dog, which revealed mild hepatomegaly and a small liver mass. An abdominal ultrasound was completed in all dogs; all were diagnosed with a right-sided unilateral adrenal mass. Three of the dogs had evidence of caudal vena caval invasion. One additional dog developed a recurrent adrenal mass with invasion of the caudal vena cava one year after initial PC diagnosis and surgical treatment. Additional ultrasonographic findings included mesenteric lymphadnopathy concerning for metastatic disease (n = 1), an incidental splenic mass (n = 1), an incidental caudal abdominal mass (n = 1), mild hepatomegaly consistent with vacuolar hepatopathy (n = 3), renal cortical hyperechogenicity consistent with degenerative renal changes (n = 3), mild pancreatic enlargement and hyperechogenicity consistent with chronic pancreatitis (n = 1), scant peritoneal effusion (n = 1), mild urinary bladder wall thickening (n = 1), and one patient with multiple ventral caudal abdominal subcutaneous nodules suspected to be metastasis from a previously diagnosed mammary carcinoma (given location and the reported subcutaneous metastatic rate of 30% for canine mammary carcinomas [31]; diagnostic sampling was not pursued).
An abdominal CT scan was completed in two dogs for further evaluation of the adrenal mass. This confirmed the presence of the suspected adrenal mass in both dogs. In addition, in one patient invasion of the adrenal mass into the phrenicoabdominal vein and right liver was identified, which was not clear on the abdominal ultrasound completed prior to the CT scan.
Two dogs were diagnosed with adrenal PC based on elevated urine catecholamine levels evaluated through Marshfield Labs. One dog had an elevated normetanephrine/creatinine ratio (2268 μg/g creatinine; reference interval [RI] 28–380 μg/g creatinine). The other had an elevated norepinephrine/creatinine ratio (0.152 μg/mg creatinine; RI 0.001–0.037 μg/mg creatinine) and an elevated dopamine/creatinine ratio (0.1 μg/mg creatinine; RI 0.00–0.031 μg/mg creatinine). The remaining three dogs did not have urine or plasma catecholamine levels evaluated.
Full staging (thoracic and abdominal imaging) was completed for all dogs, which revealed that at diagnosis three dogs had evidence of suspect metastatic disease. One dog had pulmonary metastatic disease based on CT (thoracic radiographs were not completed). The remaining four dogs were free of pulmonary metastatic disease based on thoracic radiographs. One dog had evidence of several enlarged mesenteric lymph nodes on ultrasound concerning for early metastatic disease (as mentioned above). CT scan identified a suspect bony lesion in L1 of one additional dog which was concerning for metastatic disease. No dogs had evidence of multiple endocrine neoplasia syndromes type 1 or 2.
Three dogs underwent surgical removal of their adrenal tumors and had a histologic diagnosis of PC. Additional surgical findings included a caudal abdominal lipoma, a splenic hematoma, and chronic hepatopathy (abnormalities noted previously on ultrasound, as described above). One dog that was treated surgically had evidence of caudal vena cava invasion at surgery, but not during the planning abdominal ultrasound. A CT scan was not completed in this dog. The three dogs that received surgical treatment also had blood pressure readings taken prior to and after surgical removal of the pheochromocytoma. Mean blood pressure prior to surgery was 135 mmHg (range 72–204 mmHg). Mean blood pressure after surgery was 113 mmHg (range 80–151 mmHg).
In the three dogs that had surgical removal of their PC, toceranib therapy was started at the time of recurrent, inoperable disease in one dog, for adjuvant treatment of incomplete surgical margins and the development of pulmonary metastatic disease in the second, and for treatment of pulmonary metastatic disease in the third. In the remaining two dogs, toceranib was given to treat inoperable measurable disease.
All dogs received toceranib at a starting target dose of 2.75 mg/kg orally, rounded up to the nearest available tablet size, every other day (n = 1) or Monday, Wednesday, and Friday (n = 4). At the time of data submission, three dogs were still receiving toceranib; two had treatment discontinued due to adverse side effects (one due to grade 2–3 lameness; one due to grade 2 diarrhea, grade 2 anorexia, grade 2 lethargy, and grade 3 liver enzyme elevations). Two of the three still receiving treatment had been on continuous toceranib for seven and eight months. The third had been on toceranib for a total of 17 months, including a one-month treatment break following the development of an elevated urine protein/creatinine ratio, which resolved after the treatment break. The two patients no longer on toceranib had been treated for a total of six and nine months. One patient was treated concurrently with metronomic cyclophosphamide (dog 5). Additional supportive medications included enalapril (n = 3), metronidazole (n = 2), maropitant (n = 1), famotidine (n = 1), s-adenosylmethionine and silybin A + B (n = 1), amlodipine (n = 1), carprofen (n = 1), gabapentin (n = 1), tramadol (n = 1), and omeprazole (n = 1).
Four dogs had a normal blood pressure prior to starting toceranib (one dog was not evaluated). During toceranib treatment, two dogs developed hypertension (defined as a mean systolic blood pressure of > 160 mmHg as previously described [32]) greater than 220 mmHg. Enalapril was started in both dogs which resulted in the normalization of the blood pressure. In both dogs enalapril was continued for the duration of toceranib therapy.
Three dogs required a treatment break, discontinuation, or decreased dose due to adverse side effects. One dog developed grade 2 diarrhea, grade 2 anorexia, grade 2 lethargy, and grade 3 liver enzyme elevations that progressed while on toceranib. Several drug holidays were pursued, which resulted in temporary control of adverse effects, but even at a lower dose the gastrointestinal signs returned and toceranib was ultimately discontinued after nine months of treatment. One dog developed grade 1 diarrhea and grade 3 proteinuria. Enalapril was started for the proteinuria and a one-month break was given. This resolved the proteinuria and toceranib was restarted at a lower dose (1.9 mg/kg PO Monday, Wednesday, Friday). One dog experienced grade 2–3 lameness which resulted in toceranib discontinuation (Table 1).
Clinical benefit (CR, PR, SD) was noted for all five dogs (Table 1). Four of the dogs treated with toceranib had SD. For these four dogs, PFI was determined to be at least 11, 18, 28, and 36 weeks. In one of these dogs, response was evaluated via an additional urine normetanephrine/creatinine ratio which showed normalization of the ratio following the start of toceranib treatment (levels decreased from 2268 μg/g creatinine to 326 μg/g creatinine; RI 28–380 μg/g creatinine). The fifth dog had a PR with a PFI of 61 weeks that as of data submission is on-going.
At the time of data submission, four dogs were still alive. One dog (dog 5) had been humanely euthanized due to progressive metastatic pulmonary disease 23 months after surgery to remove the primary PC, and 11 months after starting toceranib therapy for metastatic disease. The dog was on a total of six months of toceranib which was discontinued five months prior to euthanasia due to lameness and negative impact on quality of life.
The aim of this retrospective study was to evaluate the biologic response of dogs with inoperable, metastatic, or recurrent PCs to standard toceranib treatment. Beyond surgical removal, which is the treatment of choice, information about adjuvant therapy is lacking. The best treatment practices for inoperable, recurrent, or metastatic tumors is also unknown. Based on this limited case series, it appears that toceranib may have biological activity in dogs with microscopic and macroscopic PCs (primary or metastatic disease), and that toceranib might be a reasonable treatment option for owners who are hesitant to pursue surgery, for tumors that are not amenable to surgical removal, and for dogs with distant metastatic disease.
Pheochromocytomas in humans and dogs are clinically similar. Optimal treatment centers on surgical removal, with limited treatment options for inoperable tumors, those that are metastatic, and those that are recurrent. In humans, intensive chemotherapy, radiation therapy, and radiopharmaceutical agents (131I-metaiodobenzylguanidine) result in palliation of symptoms, but do not have an impact on survival [16]. Tyrosine kinase inhibitors that target c-KIT, FLT3, RET, VEGFR 1 and 2, or PDGFRβ appear to have the best biological response, reported to be around 60% [16, 17, 19, 20].
In humans, hereditary germline mutations and mutations in the von Hippel-Lindau (VHL) gene lead to the development of multiple neuroendocrine tumors including PCs [17]. An abnormally functioning VHL gene allows the activation of hypoxia-inducible transcription factors (HIF) which in turn promotes cell growth, angiogenesis, cell survival, and activation of VEGF and PDGF [33]. Similarly, mutations in succinate dehydrogenase (SDH) subunits B and D lead to the activation of HIF and the development of aggressive PCs [1]. Blockade of these mutations with small molecule inhibitors such as sunitinib via the VEGFR cell signaling pathway have led to improved quality of life, tumor size reduction, and control of PC-induced clinical signs such as hypertension [17].
One study has evaluated canine PCs, and the related paraganglioma, for SDH mutations. In that study 50% of PCs (3/6) had germline mutations in SDH, indicating that the disease may have some genetic similarities to humans [34]. Canine VHL mutations have been evaluated in canine renal carcinoma [35], but not yet in PCs, to the authors' knowledge. However, due to the evidence of SDH mutations and similar pathogenesis, it seems reasonable to conclude that human and canine PCs may be similar in their development, and thus treatment with similar TKIs blocking the VEGFR pathway may offer a therapeutic advantage for our canine patients.
Despite these similarities, the reported treatment of PCs in dogs has been largely limited to surgical removal. One case report describes the use of the radiopharmaceutical 131I-metaiodobenzylguanidine for an inoperable PC in a Yorkshire terrier [36]. 131I-metaiodobenzylguanidine is an alkyl-guanidine derivative with a molecular structure similar to norepinephrine. Selective uptake by a PC will occur after intravenous administration. The dog experienced stable disease for one and a half months after the first injection, but five months later developed progressive disease. A second injection was administered but the patient died three weeks later, likely due to compression-induced bowel ischemia [32]. To the authors' knowledge, there are no reported studies of chemotherapy or toceranib for the treatment of canine PCs.
Toceranib phosphate is an oral TKI approved for the use in dogs with Patnaik grade II or III, recurrent, cutaneous mast cell tumors with or without regional lymph node involvement. However, it appears to have efficacy against multiple tumors types, including various neuroendocrine tumors [30]. It is known to block multiple receptors including VEGFR and PDGFR [21] that stimulate angiogenesis, a known driver of human PCs.
Three dogs developed grade 1 or 2 clinical toxicities, which is in keeping with the previously reported toxicity rate for toceranib of 77.6% [30]. In addition, the toxicities observed, such as diarrhea, decreased appetite, lameness/muscle weakness, proteinuria, and hypertension, were those previously associated with toceranib [30, 32]. Neutropenia was not reported in this group of dogs. Two dogs had effects that were severe enough to warrant discontinuation of toceranib, and an additional patient required a significant dose reduction due to grade 3 proteinuria. In a recent study evaluating the use of toceranib in solid tumors, 20% of patients required a drug holiday or dose reduction, although this reduction did not appear to affect efficacy [37]. The number of dogs in this study that required discontinuation of treatment was much higher, but that is likely due to low patient numbers and lack of statistical power.
Two dogs developed hypertension, one of which was the same dog that developed grade 3 proteinuria. Hypertension is a known side effect of toceranib and has previously been reported to occur in 37% of treated dogs [32]. Hypertension is also a well-known side effect in humans treated with sunitinib. In a systematic review of the side effects associated with TKIs for the treatment of gastrointestinal stromal tumors, which inherently should not cause hypertension like PCs, 36% of human patients developed hypertension while on sunitinib [38]. In addition, in a study of humans with PC and paragangliomas treated with sunitinib, 82% had hypertension at presentation, and 35% had exacerbation of their hypertension while on sunitinib [17]. The underlying pathogenesis of TKI-induced hypertension is unknown. Prevailing theories include: (1) VEGF blockade, which prevents nitric oxide synthetase production of nitric oxide, allowing endothelin driven vasoconstriction; (2) decreased VEGF which may remodel capillaries and lead to endothelial dysfunction; or perhaps (3) TKIs may induce tumor cell apoptosis, leading to release of stored catecholamines and thus hypertension [39]. Recently, it has been determined that the development of hypertension while on a TKI is a biomarker of efficacy in some human patients treated with sunitinib [40]. In the current study, the two dogs that developed hypertension after starting treatment with toceranib both had a prolonged PFI (28 weeks and 61 weeks, respectively), and include the one dog that had a PR. One could make the argument that the development of hypertension may infer a more robust and durable response to toceranib.
There are many limitations to the current study due to its retrospective nature and small patient numbers. Histopathologic confirmation of a PC diagnosis was not obtained in all dogs. However, this is often the case in practice as a presurgical presumptive diagnosis of PC is frequently based on clinical signs and abdominal imaging alone [1, 2, 8]. The addition of urine normetanephrine/creatinine ratio measurement may aid in the diagnosis of pheochromocytoma, allowing for appropriate targeted therapy. However, sensitive and specific reference ranges have not been established to confirm the diagnosis of a PC in all clinical situations [23,24,25,26,27]. In addition, this diagnostic is not readily available at most laboratories (available, to the authors' knowledge, through Marshfield Labs, ARUP Labs, and some local human hospitals). Similarly, metastatic disease, although suspected in several dogs, was not confirmed at the time of development or on necropsy. In addition, the natural course of this cancer in these dogs prior to diagnosis and the impact of toceranib on that natural progression, is unknown.
One dog received metronomic cyclophosphamide in addition to the toceranib. Although cyclophosphamide is used to treat humans with PC in a combination protocol with vincristine and dacarbazine, use as a single agent has not been reported [41]. In addition, low-dose metronomic cyclophosphamide (used in the dog reported herein), has not been evaluated for efficacy in human or canine PC. The impact of the addition of cyclophosphamide on this dog's outcome is unknown, but may have positively contributed to the stable disease observed (dog 5). Therefore, given these caveats, it is impossible to definitively conclude that toceranib has clinical benefit for canine PCs.
Despite the aforementioned limitations, this study suggests that toceranib may offer clinical benefit to dogs with PCs. Additional studies investigating the presence of germline mutations similar to those identified in humans could help to support this conclusion. Furthermore, prospective studies are needed to better elucidate the potential role of toceranib in the treatment of both macroscopic and microscopic PCs.
Clinical benefit
CR:
Complete response
HIF:
Hypoxia-inducible transcription factors
PCs:
Pheochromocytomas
PD:
Progressive disease
PDGFRβ:
Platelet-derived growth factor receptor-β
PFI:
Progression-free interval
Partial response
RI:
Reference interval
Stable disease
SDH:
Succinate dehydrogenase
VEGFRs:
VHL:
von Hippel-Lindau gene
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The authors would like to thank doctors Antony Moore, Karen Oberthaler, Sharon Shor, and Carrissa Wood, for contributing dogs to this study.
No third-party support or funding was received in connection with this study.
VCA Veterinary Referral and Emergency Center, Norwalk, CT, USA
Margaret L. Musser & Kathryn L. Taikowski
Present address: Iowa State University College of Veterinary Medicine, Ames, IA, USA
Margaret L. Musser & Chad M. Johannes
Present address: Ohio State University College of Veterinary Medicine, Columbus, OH, USA
Kathryn L. Taikowski
VCA Clinical Studies, Los Angeles, CA, USA
Philip J. Bergman
Margaret L. Musser
Chad M. Johannes
MLM, KLT, and PJB designed this retrospective study. MLM and KLT supervised case information collection and data analysis. MLM and KLT wrote the manuscript. MLM, KLT, CMJ, and PJB assisted in writing and final editing of the manuscript. All authors read and approved the final manuscript.
Correspondence to Margaret L. Musser.
Not applicable – retrospective records review.
CMJ is a former employee of Pfizer Animal Health and has served as a member of the Zoetis Inc. (formerly Pfizer Animal Health) Oncology Advisory Board and occasionally received honoraria for these activities. PJB is a Palladia Advisory Board member and has ongoing studies sponsored by Zoetis. The remaining authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Musser, M.L., Taikowski, K.L., Johannes, C.M. et al. Retrospective evaluation of toceranib phosphate (Palladia®) use in the treatment of inoperable, metastatic, or recurrent canine pheochromocytomas: 5 dogs (2014–2017). BMC Vet Res 14, 272 (2018). https://doi.org/10.1186/s12917-018-1597-7
Pheochromocytoma
Toceranib
Submission enquiries: bmcveterinaryresearch@biomedcentral.com


Aging Boomers and healthcare reform are helping physical therapy to become a job growth leader in the United States. With life expectancy reaching 79.8 years in 2013, there is a growing need for physical therapists to help boomers to stay fit and healthy throughout their senior years. Additionally, healthcare reform is adding millions of newly-insured patients, some of whom are going to require physical therapy services.
Chronic pain is another contributor to the growth of physical therapy jobs. A study published by the National Institutes of Health (NIH) revealed that chronic pain affects nearly a third of U.S. adults. Additionally, it was found that chronic pain increases with age; so again, boomers will require additional physical therapy care.
The Bureau of Labor Statistics (BLS) forecasts that 73,500 physical therapy jobs will be created in the 10-year period from 2012 to 2022. That translates into a 36% growth rate for the 10-year period or an average of 3.6% per year.
Physical therapy salaries increase dramatically after just five years of experience.
A typical physical therapist salary is between $71,520 and $80,000 per year.
Hourly wages for physical therapists average $35 per hour.
Industry researcher and business intelligence provider, IBISWorld has an even more optimistic forecast, calling for an annual growth rate of 4.3% for physical therapist jobs until 2016.
Physical therapy centers will increase from 105,587 in 2011 to 123,351 in 2016, a 14.4% growth rate.
Revenue growth for physical therapy will grow at 4.8% annually.
Total physical therapy jobs will reach 327,851 by 2016 an increase of 123,651 from 2012 – more than 50,000 jobs higher than the BLS predicts in 2022.
Therapist Careers Nationwide American Traveler Allied specializes in nationwide career opportunities for Physical Therapists, Occupational Therapists, Respiratory Therapists, PTAs, Speech Language Pathologists and other allied professionals. We staff Outpatient Centers, Rehab Centers, skilled nursing facilities, and top rehabilitation hospitals nationwide. Experienced physical therapists are currently in high demand on the West Coast with both permanent and travel positions available; including therapist jobs in Arizona and surrounding areas.
Healthcare facilities in California are also trying to fill physical therapy positions and offer some of the highest pay rates in the nation coupled with a comprehensive benefits package. The application process is quick and easy, so apply online now or call 1-800-617-0608 to speak to one of our highly trained consultants.


Located in Calonge, Villa Calonge 1 offers an outdoor pool. This self-catering accommodation features WiFi. Accommodation will provide you with a balcony. There is a full kitchen with a dishwasher and a microwave. Extras include a washing machine, a fireplace and a private pool.
At Villa Calonge 1 you will find barbecue facilities. The property offers free parking.


text:
Diocese of Rockville Centre Department of Education
Our Lady Queen of Martyrs
St. Elizabeth of Hungary
St. Hugh of Lincoln
St. Philip of Neri
Middle School ELA
Middle School Religion
Paul Effman Band Program
IDEAL School Uniforms
CMSAA Sports
Faculty and Accreditation
Open House and Admissions
Tuition/Fees
Tomorrow's HOPE
Quick View 2020 - 2021 Calendar
Trinity Regional School
Welcome to Trinity Regional School!
Phone Email Instagram Twitter Facebook
Welcome to Middle School Religion!
Mrs. Tomasello is excited to be joining the esteemed teaching community at Trinity Regional School teaching 6th, 7th, and 8th grade Religion classes. Mrs. Tomasello earned her Bachelor of Arts degree from SUNY Old Westbury and her Master of Science degree from CW Post in Elementary Education. She also pursued a post-graduate education in Teaching English as a Second Language. Mrs. Tomasello previously taught 7th and 8th grades at another Catholic school on Long Island, as well as English classes to young adults for over a decade.
6th grade students will dive into the Old Testament to learn how God reveals himself in scripture and tradition. We will understand our role as part of a family, Church, and community, while further developing our relationship with God!
7th grade students will discover the teachings of Jesus Christ through the Christian scriptures, and develop an understanding of stewardship as we deepen our relationship with God.
8th grade students will gain new insight into the history of the Catholic Church. We will learn to appreciate our roles in our Church community, and understand that all people are called to further their relationship with God by living the Good News of the Gospel.
All classes will explore the role, function, and importance of a parish. Each of the six parishes in the Trinity Regional School region will be discussed. Students also will be completing monthly Mass Reflections and service projects throughout the year.
OFFICIAL NOTICE Schools of the Diocese of Rockville Centre admit students of any race to all the rights, privileges, programs and activities generally accorded or made available to students at the schools and that the schools do not discriminate on the basis of race in administration of their education policies, scholarship and loan programs, and athletic and other school-administered programs.
1025 Fifth Ave., East Northport, NY 11731
E-mail: trsoffice9346@trinityregional.org

redpajama_set_name: RedPajamaCommonCrawl


The Practice understands that your privacy is important to you and that we care about how your personal data is used. We respect and value the privacy of all of our patients/clients and will only collect and use personal data in ways that are described here, and in a way that is consistent with our obligations and your rights under the law.
Type of business: Provides infrastructure for self employed practitioners to operate micro businesses.
The right to have your personal data rectified if any of your personal data held us inaccurate or incomplete. Please contact us using the details in Part 11 to find out more.
Rights relating to automated decision-making and profiling. We do not use your data in this way.
Other medical intermediaries including GPs, Consultants.
Support and manage your treatment.
To communicate with you regarding appointments, responding to emails or calls from you.
To communicate with you regarding payment for treatment either direct or through medical intermediaries and insurance companies.
To communicate with other medical intermediaries directly connected with your treatment and with your permission.
We will not keep your personal data for any longer than is necessary in light of the reason(s) for which it was first collected. Your personal data will therefore be kept for eight years in line with the professional bodies/Associations including General Chiropractic Council, General Osteopathy Council, Chartered Society of Physiotherapists who demand records are kept for at least 6 years.
Medical Insurance companies authorised by you.
Other medical practitioners authorized by you.
If any personal data is transferred outside of the EEA, (in the event you are using a medical insurance company or intermediary based outside the UK) we will take suitable steps in order to ensure that your personal data is treated just as safely and securely as it would be within the UK and under the GDPR.


text:
Q: SwiftUI "Generic parameter 'Data' could not be inferred" when referencing variables from within ForEach So for some reason when I try to reference a variable within my ForEach it give me the following error: Generic parameter 'Data' could not be inferred, Explicitly specify the generic arguments to fix this issue"
I've really got no clue why this is throwing an error, it seems pretty straightforward to me but im stuck
    struct OptionsScrollView: View {

    @State var scrollOptions = [
        "test1",
        "test2",
        "test3"
    ]
    @State var optionHeight = 50

var body: some View {
    GeometryReader{outerGeo in

        ScrollView{

            VStack{
                ForEach(self.scrollOptions.indices) {i in

                    GeometryReader {optionGeo in

                        Text( self.scrollOptions[i] )

                    } // end optionGeo
                        .frame(width: 100, height: self.optionHeight)
                        //                         ^^^^^^^^^^^^^^^^^
                        //                         adding this gives me the error

                } // end ForEach

            } // end VStack

        } // end ScrollView

    } // end outerGeo
    }

}

A: Removing the GeometryReader above my ScrollView fixed my issue, not sure why!

A: correct this:   @State var optionHeight : CGFloat = 50
-> compiler assumes optionHeight is an Int, if you dont tell him ;)

redpajama_set_name: RedPajamaStackExchange


The psychological well being of elderly individuals in an institutional setting.
Paper copy at Leddy Library: Theses & Major Papers - Basement, West Bldg. / Call Number: Thesis1975 .R72. Source: Masters Abstracts International, Volume: 40-07, page: . Thesis (M.H.K.)--University of Windsor (Canada), 1975.
Roberts, Stephen M., "The psychological well being of elderly individuals in an institutional setting." (1975). Electronic Theses and Dissertations. 4184.


text:
Air Products announces a new licensing agreement with Air Liquide on hydrogen fueling
By JJ Koczan2016-06-02T21:39:00+01:00
Air Products today announced that it has signed an agreement to provide a technology license allowing Air Liquide Advanced Technologies US LLC to practice the patented Air Products technology incorporated in the Society of Automotive Engineers (SAE) J2601 hydrogen fueling protocol.
Air Products makes such hydrogen fueling technology licenses available for use around the world under fair, reasonable, and non-discriminatory (FRAND) terms. Consistent with its commitment to the SAE, Air Products will provide licenses to anyone seeking to use the patented technology as part of a fueling station project employing the J2601 protocol.
Related: Air Products brings first H2 station on-stream in Japan
"We are very proud of our accomplishments in the hydrogen fueling and infrastructure marketplace and believe this license is recognition of our capabilities. We will accommodate additional licenses for our technology as the hydrogen fueling network in the United States and around the world continues to expand," said Ed Kiczek, Global Business Director, Hydrogen Energy Systems at Air Products.
Bringing SmartFuel forward
Air Products uses its patented hydrogen fueling technology in conjunction with the J2601 protocol at its own SmartFuel® stations, and also those built for other customers. SmartFuel stations worldwide provide hydrogen fueling at 700 bar (10,000 psi).
Air Products has available several SmartFuel stations incorporating modular and expandable technology and a global patent portfolio, with additional patents pending, related to the advancements to be deployed under this protocol.
What is a hydrogen fuel cell?
Consisting of a single electron orbiting a single proton, hydrogen is the simplest element in the universe – but this simple element can release almost three-times more energy than natural gas. The fact that hydrogen fuel comes with zero carbon emissions (its only by-product is water and heat), has made ...
Air Liquide announces Northeast US hydrogen stations
Air Liquide expects to open hydrogen fueling stations in New York, Connecticut and Massachusetts by early next year.
Air Liquide installs H2 station in forklift warehouse
Tier One corporation, Air Liquide, has deployed a hydrogen (H2) station in Prelocentre's warehouse in Saint-Cyr-en-Val, France, to recharge its onsite forklifts.


text:
The Hatfields & the McCoys...in Memphis Tn
http://bit.ly/1rMIVa1
MEMPHIS, Tenn. — Families are at war in southwest Memphis neighborhood. Some are even calling it a modern day Hatfields and McCoys battle.
Police arrested a man they say shot at his neighbor over his tall grass.
Darrel Brock is facing an aggravated assault charge, but his wife says her husband was the one being threatened.
Steve Bush lives on Tulip Road, and said Brock and his neighbors across the street never got along. Tuesday night, it took a dangerous turn.
"The guy came from behind his house, and he had a pistol," Bush said of Brock. "I heard a shot."
Bush said his family has lived on Tulip Road for generations. Almost the whole street is related. So when Brock moved in, so did trouble.
Bush said Brock put up cameras and no trespassing signs and was anything but friendly.
"He just wants to take control," Bush said. "The kids can't play in the street, and he doesn't even want you walking by his house."
Police said Brock shot at his neighbor, Toney Harris, Tuesday night and threatened to kill him. They said the argument started when Brock complained about Harris' grass being too long.
Harris then went to the yard next to Brock's to see if he could find any code violations to report.
"That's the way it is…The Hatfields and the McCoys," Bush said of the two families.


I had a look around and there are similar posts but I didn't see effective solutions (maybe there are but couldn't find them).
When I run it, I get the hourglass next to the mouse pointer for a couple of seconds, then it disappears....what am I doing wrong ?
The drive is partitioned with Vista on a partition and XP on the other...it boots in XP.
In the past I already used EasyBCD without problems...now I just re-installed XP.
Can you repair the Windows Vista boot so you can get into Windows Vista with the Windows Vista recovery disk and install Easy BCD in Windows Vista? Then make an entry for Windows Vista in easy That BCD.
Hi oggie, welcome to NeoSmart.
I assume you're running EasyBCD on Windows XP right now and you get the hourglass thing?
1) In the task manager (ctrl+shift+esc) do you see either "EasyBCD.exe" or "BootGrabber.exe" or "bcdedit.exe" running?
2) In the event viewer (start | run | eventvwr.msc) in the "Windows Logs" -> "Applications" do you see any errors around the same time you launched EasyBCD?
Something to do with your hardware configuration, I presume.
And copy and paste the output here in a reply?
Where are you located, btw? Just wondering because I'm +2 UTC and you seem to be +1 UTC? Usually get people in a completely different timezone, night & day.
I am in Malta - and you ?
Something else : very, very strange....just tried EasyBCD on my other computer (which i am now using) - same problem !
Just tried "bootgrabber.exe /list" - answer was "No active partition detected on disk1" ??
That message is normal, it is only a "warning" and not an error.
But did BootGrabber.exe complete running or did it hang after printing that message?
Oh, and I'm in Jordan.
The DOS prompt does not come - seems it remains busy but shows no sign of life !
Yeah, that's what I feared.
I suppose a screenshot of Control Panel | Admin Tool | Computer Management | Disk Management would help.
I can't from this computer but will be on other in about 1 hr - is it ok ?
Oh wow... That's more drives than even I have!
I'm not surprised something went wrong with that complex a setup.
Did BootGrabber only print that one line? I'll probably have to send you a build with extra logging or something to try and pin down this issue.
Don't be impressed by the drives : the computer's drive is 320gB - partitioned in 3 - XP, Vista and data. The others are network drives ; 200gB and 400gB, both partitioned in two in an attempt to make finding something easier....did it work ?...so so..
Yes, that's all it said - not very informative, eh ?
Something very strange happened : I tried EasyBCD and,as expected, nothing happened. I started Task Manager, found BootGrabber.exe and "End Task" - as soon as I ended the task, EasyBCD asked if I want to load a bootloader. I chose "yes" and when asked where to get it from, I cancelled...next EasyBCD started ! I couldn't do much as apparently my boot.ini is missing.....does this make any sense to you ?
BTW, I tried it again to see if it was a one-off freak accident - it was not ! Any ideas ?
At startup, EasyBCD launches BootGrabber.exe, a super-low-level helper application that retrieves information about the attached drives on your system. BootGrabber.exe and its info are required in order to add a Windows NT/2k/XP/2k3 entry and certain types of Linux entries.
EasyBCD waits for BootGrabber.exe to get this info, report back, and exit. Without this info, you'll be unable to add an XP entry or said Linux entries.
If all you want to do is write the MBR or add a Vista/7 entry, EasyBCD will work in this mode. But seeing as you need some XP-related EasyBCD magic, we're going to need to figure out what's stopping BootGrabber on your system. I'll upload a copy of BG with advanced debug logging soon, and maybe we can find out what is causing these problems.
By what i understood, BootGrabber.exe looks for a file with a .BCD extension.....where should that be ? If it should be in root of C:, it's not there - could it be ?
No - BootGrabber gets information about the disks, and has nothing to do with the "BCD not found" error which is a whole 'nother issue.