Healthcare utilization and costs among intracranial meningioma patients during long-term follow-up.

PURPOSE: Few studies have reported on healthcare utilization and costs for intracranial meningioma patients, while the tumor and its treatment profoundly affect patients' functioning and well-being. Here we evaluated healthcare utilization and costs, including their determinants. METHODS: A multicenter cross-sectional study of adult meningioma patients ≥ 5 years after intervention. Patients completed three validated patient-reported outcome measures (PROMs) assessing patients 'functioning and wellbeing (SF-36, EORTC QLQ-BN20, and HADS) and a study-specific questionnaire assessing healthcare utilization over the previous twelve months. Healthcare costs of the twelve months prior were calculated using reported healthcare utilization ≥ 5 years after intervention by the Dutch Manual for Economic Evaluation in Healthcare. Determinants for healthcare utilization and costs were determined with regression analyses. RESULTS: We included 190 patients with WHO grade I or II meningioma after a mean follow-up since intervention of 9.2 years (SD 4.0). The general practitioner (80.5%), physiotherapist (37.9%), and neurologist (25.4%) were visited most often by patients. Median annual healthcare costs were €871 (IQR €262-€1933). Main contributors to these costs were medication (45.8% of total costs, of which anti-seizure medication was utilized most [21.6%]), specialist care (17.7%), and physiotherapy (15.5%). Lower HRQoL was a significant determinant for higher healthcare utilization and costs. CONCLUSION: In patients with meningioma, medication costs constituted the largest expenditure of total healthcare costs, in particular anti-seizure medication. Particularly a lower HRQoL was a determinant for healthcare utilization and costs. A patient-specific approach aimed at improving patients' HRQoL and needs could be beneficial in reducing disease burden and functional recovery.

Costs and Its Determinants in Pituitary Tumour Surgery.

Purpose: Value-based healthcare (VBHC) provides a framework to improve care by improving patient outcomes and reducing healthcare costs. To support value-based decision making in clinical practice we evaluated healthcare costs and cost drivers in perioperative care for pituitary tumour patients. Methods: We retrospectively assessed financial and clinical data for surgical treatment up to the first year after surgery of pituitary tumour patients treated between 2015 and 2018 in a Dutch tertiary referral centre. Multivariable regression analyses were performed to identify determinants of higher costs. Results: 271 patients who underwent surgery were included. Mean total costs (SD) were €16339 (13573) per patient, with the following cost determinants: surgery time (€62 per minute; 95% CI: 50, 74), length of stay (€1331 per day; 95% CI 1139, 1523), admission to higher care unit (€12154 in total; 95% CI 6413, 17895), emergency surgery (€10363 higher than elective surgery; 95% CI: 1422, 19305) and postoperative cerebrospinal fluid leak (€14232; 95% CI 9667, 18797). Intradural (€7128; 95% CI 10421, 23836) and combined transsphenoidal/transcranial surgery (B: 38494; 95% CI 29191, 47797) were associated with higher costs than standard. Further, higher costs were found in these baseline conditions: Rathke's cleft cyst (€9201 higher than non-functioning adenoma; 95% CI 1173, 17230), giant adenoma (€19106 higher than microadenoma; 95% CI 12336, 25877), third ventricle invasion (€14613; 95% CI 7613, 21613) and dependent functional status (€12231; 95% CI 3985, 20477). In patients with uncomplicated course, costs were €8879 (3210) and with complications €17551 (14250). Conclusions: Length of hospital stay, and complications are the main drivers of costs in perioperative pituitary tumour healthcare as were some baseline features, e.g. larger tumors, cysts and dependent functional status. Costs analysis may correspond with healthcare resource utilization and guide further individualized care path development and capacity planning.

Clinical and radiographic assessment of peripheral joints in controlled acromegaly.

PURPOSE: Acromegalic arthropathy is a well-known phenomenon, occurring in most patients regardless of disease status. To date, solely hips, knees, hands, and spinal joints have been radiographically assessed. Therefore, this study aimed to assess the prevalence of joint symptoms and radiographic osteoarthritis (OA) of new, and established peripheral joint sites in well-controlled acromegaly. METHODS: Fifty-one acromegaly patients (56% female, mean age 64 ± 12 years) in long-term remission for 18.3 years (median, IQR 7.2-25.4) were included. Nineteen patients currently received pharmacological treatment. Self-reported joint complaints were assessed using standardized interviews. Self-reported disability of the upper and lower limbs, and health-related quality of life (HR-QoL) were evaluated using validated questionnaires. Radiographic OA [defined as Kellgren & Lawrence (KL) ≥ 2] was scored using (modified) KL methods. RESULTS: Radiographic signs of OA were present in 46 patients (90.2%) with ≥ 2 joints affected in virtually all of these patients (N = 44; 95.7%). Radiographic MTP1 OA was as prevalent as radiographic knee OA (N = 26, 51.0%), and radiographic glenohumeral OA was similarly prevalent as hip OA [N = 21 (41.2%) vs. N = 24 (47.1%)]. Risk factors for radiographic glenohumeral OA were higher pre-treatment IGF-1 levels [OR 1.06 (1.01-1.12), P = 0.021], and current pharmacological treatment [OR 5.01 (1.03-24.54), P = 0.047], whereas no risk factors for MTP1 joint OA could be identified. CONCLUSION: Similar to previously-assessed peripheral joints, clinical and radiographic arthropathy of the shoulder and feet were prevalent in controlled acromegaly. Further studies on adequate management strategies of acromegalic arthropathy are needed.

Disease and Treatment-Related Burden in Patients With Acromegaly Who Are Biochemically Controlled on Injectable Somatostatin Receptor Ligands.

Medical treatment for acromegaly commonly involves receiving intramuscular or deep subcutaneous injections of somatostatin receptor ligands (SRLs) in most patients. In addition to side effects of treatment, acromegaly patients often still experience disease symptoms even when therapy is successful in controlling GH and IGF-1 levels. Symptoms and side effects can negatively impact patients' health-related quality of life. In this study, we examine the disease- and treatment-related burden associated with SRL injections as reported through the use of the Acromegaly Treatment Satisfaction Questionnaire (Acro-TSQ ©) and clinician-reported symptom severity through the Acromegaly Index of Severity (AIS). Patients included in this analysis were enrolled in a randomized phase 3 study, were biochemically-controlled (an IGF-1 < 1.3 × the upper limit of normal [ULN] and average GH < 2.5 ng/ml) and receiving SRL injections for ≥6 months with a stable dose of either long-acting octreotide or lanreotide monotherapy for ≥4 months. The sample (N = 91) was 65% female, 91% Caucasian, with a mean [standard deviation (SD)] age of 53 (1) years. Two-thirds of patients reported that they still experience acromegaly symptoms; 82% of these said they experience symptoms all of the time. Three-fourths experienced gastrointestinal (GI) side effects after injections, and 77% experienced treatment-related injection site reactions (ISRs). Patients commonly reported that these interfered with their daily life, leisure, and work activities. Those with higher symptom severity, as measured by the AIS, scored significantly worse on several Acro-TSQ domains: Symptom Interference, GI Interference, Treatment Satisfaction, and Emotional Reaction. Despite being biochemically controlled with injectable SRLs, most patients reported experiencing acromegaly symptoms that interfere with daily life, leisure, and work. GI side effects and ISRs were also common. This study highlights the significant disease burden that still persists for patients with acromegaly that have achieved biochemical control with the use of injectable SRLs.

Sleep characteristics across the lifespan in 1.1 million people from the Netherlands, United Kingdom and United States: a systematic review and meta-analysis.

We aimed to obtain reliable reference charts for sleep duration, estimate the prevalence of sleep complaints across the lifespan and identify risk indicators of poor sleep. Studies were identified through systematic literature search in Embase, Medline and Web of Science (9 August 2019) and through personal contacts. Eligible studies had to be published between 2000 and 2017 with data on sleep assessed with questionnaires including ≥100 participants from the general population. We assembled individual participant data from 200,358 people (aged 1-100 years, 55% female) from 36 studies from the Netherlands, 471,759 people (40-69 years, 55.5% female) from the United Kingdom and 409,617 people (≥18 years, 55.8% female) from the United States. One in four people slept less than age-specific recommendations, but only 5.8% slept outside of the 'acceptable' sleep duration. Among teenagers, 51.5% reported total sleep times (TST) of less than the recommended 8-10 h and 18% report daytime sleepiness. In adults (≥18 years), poor sleep quality (13.3%) and insomnia symptoms (9.6-19.4%) were more prevalent than short sleep duration (6.5% with TST < 6 h). Insomnia symptoms were most frequent in people spending ≥9 h in bed, whereas poor sleep quality was more frequent in those spending <6 h in bed. TST was similar across countries, but insomnia symptoms were 1.5-2.9 times higher in the United States. Women (≥41 years) reported sleeping shorter times or slightly less efficiently than men, whereas with actigraphy they were estimated to sleep longer and more efficiently than man. This study provides age- and sex-specific population reference charts for sleep duration and efficiency which can help guide personalized advice on sleep length and preventive practices.

Healthcare utilization and costs among prolactinoma patients: a cross-sectional study and analysis of determinants.

PURPOSE: Prolactinomas are the most prevalent functioning pituitary adenomas. They affect gonadal function as well as health-related quality of life (HRQoL). This study aimed to report healthcare utilization and costs, including their determinants, for prolactinoma patients. METHODS: Cross-sectional study of 116 adult prolactinoma patients in chronic care in a Dutch tertiary referral center. Patients completed four validated questionnaires, assessing healthcare utilization and costs over the previous 12 months (Medical Consumption Questionnaire), disease bother and needs (Leiden Bother and Needs Questionnaire Pituitary), HRQoL (Short Form-36), and self-reported health status (EuroQol 5D). Regression analyses were used to assess associations between disease-related characteristics and healthcare utilization and costs. RESULTS: Mean age was 52.0 years (SD 13.7) and median follow-up was 15.0 years (IQR 7.6-26.1). Patients visited the endocrinologist (86.2%), general practitioner (37.9%), and ophthalmologist (25.0%) most frequently. Psychological care was used by 12.9% of patients and 5% were admitted to hospital. Mean annual healthcare costs were €1928 (SD 3319), mainly for pituitary-specific medication (37.6% of total costs), hospitalization (19.4%) and specialist care (16.1%). Determinants for higher healthcare utilization and costs were greater disease bother and needs for support, lower HRQoL, elevated prolactin, and longer disease duration, while tumor size, hypopituitarism and adrenal insufficiency were not significantly associated with healthcare utilization and costs. CONCLUSION: Healthcare utilization and costs of prolactinoma patients are related to patient-reported HRQoL, bother by disease and needs for support. Therefore, addressing patients' HRQoL and needs is a way forward to improve efficiency of care and patients' health status.

The burden of disease for pituitary patients.

Pituitary diseases are rare conditions with severe chronic multiorgan and multisystemic morbidity requiring complex multidisciplinary treatment and usually life-long drug treatment. Most cases are caused by functioning or non-functioning pituitary adenoma. From the patient's perspective, the burden of disease is caused by the tumour itself and associated compression symptoms, interventions, hormone excess and deficiencies, systemic manifestations of these endocrine abnormalities and general psychosocial issues that can manifest in patients with a chronic condition. In this review, patient burden is classified according to classic endocrine syndromes, with burden at diagnosis and after long-term remission, and also within the framework of value-based health care and the conceptual model of wellbeing. The recently developed patient-reported outcome measurement tool that helps to evaluate burden of patients is also discussed.

Toward Value Based Health Care in pituitary surgery: application of a comprehensive outcome set in perioperative care.

OBJECTIVE: Although widely advocated, applying Value Based Health Care (VBHC) in clinical practice is challenging. This study describes VBHC-based perioperative outcomes for patients with pituitary tumors up to 6 months postoperatively. METHODS: A total of 103 adult patients undergoing surgery were prospectively followed. Outcomes categorized according to the framework of VHBC included survival, degree of resection, endocrine remission, visual outcome (including self-perceived functioning), recovery of pituitary function, disease burden and health-related quality of life (HRQoL) at 6 months (Tier 1); time to recovery of disease burden, HRQoL, visual function (Tier 2); permanent hypopituitarism and accompanying hormone replacement (Tier 3). Generalized estimating equations (GEEs) analysis was performed to describe outcomes over time. RESULTS: Regarding Tier 1, there was no mortality, 72 patients (70%) had a complete resection, 31 of 45 patients (69%) with functioning tumors were in remission, 7 (12%, with preoperative deficits) had recovery of pituitary function and 45 of 47 (96%) had visual improvement. Disease burden and HRQoL improved in 36-45% at 6 months; however, there were significant differences between tumor types. Regarding Tier 2: disease burden, HRQoL and visual functioning improved within 6 weeks after surgery; however, recovery varied widely among tumor types (fastest in prolactinoma and non-functioning adenoma patients). Regarding Tier 3, 52 patients (50%) had persisting (tumor and treatment-induced) hypopituitarism. CONCLUSIONS: Though challenging, outcomes of a surgical intervention for patients with pituitary tumors can be reflected through a VBHC-based comprehensive outcome set that can distinguish outcomes among different patient groups with respect to tumor type.

The Association between Habitual Sleep Duration and Sleep Quality with Glycemic Traits: Assessment by Cross-Sectional and Mendelian Randomization Analyses.

Evidence on whether habitual sleep duration and sleep quality are associated with increased insulin resistance is inconsistent. Here, we investigated the associations between different measures of habitual sleep with glycemic traits through cross-sectional and Mendelian randomization (MR) analyses. We assessed the associations of sleep duration and sleep quality with glycemic traits using multivariable linear regression models adjusted for potential confounders in 4672 middle-aged (45-65 years; 48% men) nondiabetic participants of the Netherlands Epidemiology of Obesity (NEO) study. Genetic variants for total, short, and long sleep duration were used as instrumental variables in MR analyses using summary-level data of glycemic traits in nondiabetic individuals (MAGIC; n = 58,074). In cross-sectional analyses, shortest sleepers (median 5.0 h of sleep per night) had 14.5% (95% confidence interval (CI): 2.0; 28.6%) higher fasting insulin level and 16.3% (95% CI: 2.7; 31.7%) higher HOMA-ß. Bad sleep quality was associated with higher insulin resistance (e.g., 14.3% (95% CI: 4.7; 24.9%) higher HOMA-IR). All these associations disappeared after adjustment for BMI and the risk of sleep apnea. MR analyses did not indicate a causal association between total, short or long sleep duration and glycemic traits. Therefore, our used measures of habitual sleep duration and sleep quality are unlikely to directly associate with insulin resistance.

Healthcare utilization and costs among patients with non-functioning pituitary adenomas.

PURPOSE: Non-functioning pituitary adenomas (NFPA) have a substantial impact on patients' health status, yet research on the extent of healthcare utilization and costs among these patients is scarce. The objective was to determine healthcare usage, associated costs, and their determinants among patients treated for an NFPA. METHODS: In a cross-sectional study, 167 patients treated for an NFPA completed four validated questionnaires. Annual healthcare utilization and associated costs were assessed through the medical consumption questionnaire (MTA iMCQ). In addition, the Leiden Bother and Needs Questionnaire for pituitary patients (LBNQ-Pituitary), Short Form-36 (SF-36), and EuroQol (EQ-5D) were administered. Furthermore, age, sex, endocrine status, treatment, and duration of follow-up were extracted from the medical records. Associations were analyzed using logistic/linear regression. RESULTS: Annual healthcare utilization included: consultation of an endocrinologist (95% of patients), neurosurgeon (14%), and/or ophthalmologist (58%). Fourteen percent of patients had ≥1 hospitalization(s) and 11% ≥1 emergency room visit(s). Mean overall annual healthcare costs were € 3040 (SD 6498), highest expenditures included medication (31%), inpatient care (28%), and specialist care (17%). Factors associated with higher healthcare utilization and costs were greater self-perceived disease bother and need for support, worse mental and physical health status, younger age, and living alone. CONCLUSION: Healthcare usage and costs among patients treated for an NFPA are substantial and were associated with self-perceived health status, disease bother, and healthcare needs rather than endocrine status, treatment, or duration of follow-up. These findings suggest that targeted interventions addressing disease bother and unmet needs in the chronic phase are needed.

Mapping AcroQoL scores to EQ-5D to obtain utility values for patients with acromegaly.

AIMS: To estimate a preference-based single index for the disease-specific instrument (AcroQoL) by mapping it onto the EQ-5D to assist in future economic evaluations. MATERIALS AND METHODS: A sample of 245 acromegaly patients with AcroQoL and EQ-5D scores was obtained from three previously published European studies. The sample was split into two: one sub-sample to construct the model (algorithm construction sample, n = 184), and the other one to confirm it (validation sample, n = 61). Various multiple regression models including two-part model, tobit model, and generalized additive models were tested and/or evaluated for predictive ability, consistency of estimated coefficients, normality of prediction errors, and simplicity. RESULTS: Across these studies, mean age was 50-60 years and the proportion of males was 36-59%. At overall level the percentage of patients with controlled disease was 37.4%. Mean (SD) scores for AcroQoL Global Score and EQ-5D utility were 62.3 (18.5) and 0.71 (0.28), respectively. The best model for predicting EQ-5D was a generalized regression model that included the Physical Dimension summary score and categories from questions 9 and 14 as independent variables (Adj. R2 = 0.56, with mean absolute error of 0.0128 in the confirmatory sample). Observed and predicted utilities were strongly correlated (Spearman r = 0.73, p < .001) and paired t-Student test revealed non-significant differences between means (p > .05). Estimated utility scores showed a minimum error of ≤10% in 45% of patients; however, error increased in patients with an observed utility score under 0.2. The model's predictive ability was confirmed in the validation cohort. LIMITATIONS AND CONCLUSIONS: A mapping algorithm was developed for mapping of AcroQoL to EQ-5D, using patient level data from three previously published studies, and including validation in the confirmatory sub-sample. Mean (SD) utilities index in this study population was estimated as 0.71 (0.28). Additional research may be needed to test this mapping algorithm in other acromegaly populations.

Patient-reported outcomes of parenteral somatostatin analogue injections in 195 patients with acromegaly.

BACKGROUND: Long-acting somatostatin analogues delivered parenterally are the most widely used medical treatment in acromegaly. This patient-reported outcomes survey was designed to assess the impact of chronic injections on subjects with acromegaly. METHODS: The survey was conducted in nine pituitary centres in Germany, UK and The Netherlands. The questionnaire was developed by endocrinologists and covered aspects of acromegaly symptoms, injection-related manifestations, emotional and daily life impact, treatment satisfaction and unmet medical needs. RESULTS: In total, 195 patients participated, of which 112 (57%) were on octreotide (Sandostatin LAR) and 83 (43%) on lanreotide (Somatuline Depot). The majority (>70%) of patients reported acromegaly symptoms despite treatment. A total of 52% of patients reported that their symptoms worsen towards the end of the dosing interval. Administration site pain lasting up to a week following injection was the most frequently reported injection-related symptom (70% of patients). Other injection site reactions included nodules (38%), swelling (28%), bruising (16%), scar tissue (8%) and inflammation (7%). Injection burden was similar between octreotide and lanreotide. Only a minority of patients received injections at home (17%) and 5% were self-injecting. Over a third of patients indicated a feeling of loss of independence due to the injections, and 16% reported repeated work loss days. Despite the physical, emotional and daily life impact of injections, patients were satisfied with their treatment, yet reported that modifications that would offer major improvement over current care would be 'avoiding injections' and 'better symptom control'. CONCLUSION: Lifelong injections of long-acting somatostatin analogues have significant burden on the functioning, well-being and daily lives of patients with acromegaly.

Quality of life (QoL) impairments in patients with a pituitary adenoma: a systematic review of QoL studies.

PURPOSE: Pituitary adenomas give rise to physical and psychological symptoms, which may persist after biochemical cure. Growing attention has been paid to quality of life (QoL) in these patients. We aimed to systematically analyze QoL assessment methods and QoL outcome in these patients. METHODS: We conducted a systematic literature search up to January 2014 in PubMed, Web of Knowledge, PsycInfo and EMBASE. RESULTS: 102 papers assessing QoL in patients with a pituitary adenoma were included. In clinical (original) studies in which QoL was the primary outcome parameter (n = 54), 19 studies combined a generic questionnaire with a disease-specific questionnaire. QoL was found to be impaired in patients with active disease relative to controls, and generally improved during biochemical cure. However, no normalization occurred, with patients with remitted Cushing's disease demonstrating the smallest improvement. Somatic factors (e.g., hypopituitarism, sleep characteristics), psychological factors (illness perceptions) and health care environment (rural vs. urban) were identified as influencing factors. Intervention studies (predominantly evaluating medical interventions) have been found to improve QoL. CONCLUSIONS: The growing number of studies assessing QoL generally described the negative impact of pituitary adenomas. QoL research in this patient group could be further elaborated by the development of disease-specific questionnaires for prolactinoma and non-functioning adenoma, consequent use of generic and disease-specific questionnaires and using a long-term (longitudinal) follow-up. Surgical and pharmacological interventions improve but not normalize QoL. We postulate that there might be margin for further improvement of QoL, for instance by using psychosocial interventions, in addition to optimal medical treatment.

Cost-effectiveness of lanreotide Autogel in treatment algorithms of acromegaly.

The introduction of effective pharmacological treatments has changed the management of acromegaly. However, chronic, life-long treatment with somatostatin analogues and/or growth hormone receptor antagonists is very expensive. We estimated the costs of treatment algorithms to control acromegaly from a Dutch perspective. We used the following assumptions: after the diagnosis of acromegaly there is a mean remaining lifespan of approximately 33 years; the success rates of surgery and somatostatin analogues in controlling the disease are approximately 60%; and the lifelong costs of different algorithms to control acromegaly in 100 patients ranged from 43 million euros (primary surgery and secondary somatostatin analogues) to 57 million euros (primary somatostatin analogues and secondary surgery) and even reached 95 million euros (medical treatment only). In algorithms that include trans-sphenoidal surgery, the lifetime treatment costs are almost 46-59% cheaper per 100 patients than in algorithms with medical treatment but without trans-sphenoidal surgery. Algorithms with primary surgery and secondary somatostatin analogs are 30% cheaper per 100 patients than algorithms with primary somatostatin analogues and secondary surgery. Per 100 patients, algorithms including lanreotide Autogel are 14-34% more expensive than algorithms including octreotide long-acting release. These life-long costs should be taken into consideration when making choices between treatment algorithms.

Current pharmacotherapy for acromegaly: a review.

Acromegaly is associated with considerable morbidity and excess mortality; however, after effective treatment, both morbidity and mortality risks improve. Growth hormone excess in acromegaly can be controlled in many patients by pharmacotherapy alone, and with a combination of transsphenoidal surgery and pharmacotherapy in almost all patients. Since the clinical introduction of pegvisomant, a growth hormone-receptor antagonist, the role of radiotherapy is restricted. This review focuses on the treatment options for acromegaly (e.g., surgery, radiotherapy and pharmacotherapy with the depot preparations of the somatostatin analogues octreotide long-acting release formulation, lanreotide slow-release formulation and lanreotide Autogel, the growth hormone antagonist pegvisomant and the dopamine agonist cabergoline). Pharmacological characteristics of these drugs and the clinical and adverse effects are discussed individually and in relation to the other treatment modalities. The evidence for biochemical goals aimed at during medical treatment and the costs of pharmacotherapy are discussed. A new treatment algorithm is proposed, in which the choice between primary medical treatment and primary surgery is individualised, dependent on adenoma size and extension, patient factors (age, preference for therapy, contraindication for surgery), surgical experience of the centre and octreotide sensitivity of the adenoma. The high cost of lifelong medical treatment, especially of pegvisomant, must be weighed against the cost of a single surgical procedure.