BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) has been shown to pose considerable clinical and economic burden; however, research quantifying the excess burden attributable to common psychiatric comorbidities of ADHD among pediatric patients is scarce. This study assessed the impact of anxiety and depression on healthcare resource utilization (HRU) and healthcare costs in pediatric patients with ADHD in the United States.
METHODS: Patients with ADHD aged 6-17 years were identified in the IQVIA PharMetrics Plus database (10/01/2015-09/30/2021). The index date was the date of initiation of a randomly selected ADHD treatment. Patients with ≥ 1 diagnosis for anxiety and/or depression during both the baseline (6 months pre-index) and study period (12 months post-index) were classified in the ADHD+anxiety/depression cohort; those without diagnoses for anxiety nor depression during both periods were classified in the ADHD-only cohort. Entropy balancing was used to create reweighted cohorts. All-cause HRU and healthcare costs during the study period were compared using regression analyses. Cost analyses were also performed in subgroups by comorbid conditions.
RESULTS: The reweighted ADHD-only cohort (N = 204,723) and ADHD+anxiety/depression cohort (N = 66,231) had similar characteristics (mean age: 11.9 years; 72.8% male; 56.2% had combined inattentive and hyperactive ADHD type). The ADHD+anxiety/depression cohort had higher HRU than the ADHD-only cohort (incidence rate ratios for inpatient admissions: 10.3; emergency room visits: 1.6; outpatient visits: 2.3; specialist visits: 5.3; and psychotherapy visits: 6.1; all p < 0.001). The higher HRU translated to greater all-cause healthcare costs; the mean per-patient-per-year (PPPY) costs in the ADHD-only cohort vs. ADHD+anxiety/depression cohort was $3,988 vs. $8,682 (p < 0.001). All-cause healthcare costs were highest when both comorbidities were present; among patients with ADHD who had only anxiety, only depression, and both anxiety and depression, the mean all-cause healthcare costs were $7,309, $9,901, and $13,785 PPPY, respectively (all p < 0.001).
CONCLUSIONS: Comorbid anxiety and depression was associated with significantly increased risk of HRU and higher healthcare costs among pediatric patients with ADHD; the presence of both comorbid conditions resulted in 3.5 times higher costs relative to ADHD alone. These findings underscore the need to co-manage ADHD and psychiatric comorbidities to help mitigate the substantial burden borne by patients and the healthcare system.

BACKGROUND: Depending on the underlying etiology and epilepsy type, the burden of disease for patients with seizures can vary significantly. This analysis aimed to compare direct and indirect costs and quality of life (QoL) among adults with tuberous sclerosis complex (TSC) related with epilepsy, idiopathic generalized epilepsy (IGE), and focal epilepsy (FE) in Germany.
METHODS: Questionnaire responses from 92 patients with TSC and epilepsy were matched by age and gender, with responses from 92 patients with IGE and 92 patients with FE collected in independent studies. Comparisons were made across the main QoL components, direct costs (patient visits, medication usage, medical equipment, diagnostic procedures, ancillary treatments, and transport costs), indirect costs (employment, reduced working hours, missed days), and care level costs.
RESULTS: Across all three cohorts, mean total direct costs (TSC: €7602 [median €2620]; IGE: €1919 [median €446], P < 0.001; FE: €2598 [median €892], P < 0.001) and mean total indirect costs due to lost productivity over 3 months (TSC: €7185 [median €11,925]; IGE: €3599 [median €0], P < 0.001; FE: €5082 [median €2981], P = 0.03) were highest among patients with TSC. The proportion of patients with TSC who were unemployed (60%) was significantly larger than the proportions of patients with IGE (23%, P < 0.001) or FE (34%, P = P < 0.001) who were unemployed. Index scores for the EuroQuol Scale with 5 dimensions and 3 levels were significantly lower for patients with TSC (time-trade-off [TTO]: 0.705, visual analog scale [VAS]: 0.577) than for patients with IGE (TTO: 0.897, VAS: 0.813; P < 0.001) or FE (TTO: 0.879, VAS: 0.769; P < 0.001). Revised Epilepsy Stigma Scale scores were also significantly higher for patients with TSC (3.97) than for patients with IGE (1.48, P < 0.001) or FE (2.45, P < 0.001). Overall Quality of Life in Epilepsy Inventory-31 items scores was significantly lower among patients with TSC (57.7) and FE (57.6) than among patients with IGE (66.6, P = 0.004 in both comparisons). Significant differences between patients with TSC and IGE were also determined for Neurological Disorder Depression Inventory for Epilepsy (TSC: 13.1; IGE: 11.2, P = 0.009) and Liverpool Adverse Events Profile scores (TSC: 42.7; IGE: 37.5, P = 0.017) with higher score and worse results for TSC patients in both questionnaires.
CONCLUSIONS: This study is the first to compare patients with TSC, IGE, and FE in Germany and underlines the excessive QoL burden and both direct and indirect cost burdens experienced by patients with TSC.

BACKGROUND: The rise of periprosthetic joint infections (PJIs) due to aging populations is steadily increasing the number of arthroplasties and treatment costs. This study analyzed the direct health care costs of PJI for total hip arthroplasty and total knee arthroplasty (TKA) in Europe.
METHODS: The databases PubMed, Scopus, Embase, Cochrane, and Google Scholar were systematically screened for direct costs of PJI in Europe. Publications that defined the joint site and the procedure performed were further analyzed. Mean direct health care costs were calculated for debridement, antibiotics, and implant retention (DAIR), one-stage, and 2-stage revisions for hip and knee PJI, respectively. Costs were adjusted for inflation rates and reported in US-Dollar (USD).
RESULTS: Of 1,374 eligible publications, 12 manuscripts were included in the final analysis after an abstract and full-text review. Mean direct costs of $32,933 were identified for all types of revision procedures for knee PJI. The mean direct treatment cost including DAIR for TKA after PJI was $19,476. For 2-stage revisions of TKA, the mean total cost was $37,980. For all types of hip PJI procedures, mean direct hospital costs were $28,904. For hip DAIR, one-stage and 2-stage treatment average costs of $7,120, $44,594, and $42,166 were identified, respectively.
CONCLUSIONS: Periprosthetic joint infections are associated with substantial direct health care costs. As detailed reports on the cost of PJI are scarce and of limited quality, more detailed financial data on the cost of PJI treatment are urgently required.

UNASSIGNED: Telemonitoring improves clinical outcomes in patients with arterial hypertension (AH) and type 2 diabetes (T2D), however, cost structure analyses are lacking. This study seeks to explore the cost structure of telemonitoring for the elderly with AH and T2D in primary care and identify factors influencing costs for potential future expansions.
UNASSIGNED: Infrastructure, operational, patient participation, and out-of-pocket costs were determined using a bottom-up approach. Infrastructure costs were determined by dividing equipment and telemonitoring platform expenses by the number of participants. Operational and patient participation costs were determined by considering patient training time, data measurement/review time, and teleconsultation time. The change in out-of-pocket costs was assessed in both groups using a structured questionnaire and 12-month expenditure data. Statistical analysis employed an unpaired sample t-test, Mann-Whitney U test, and chi-square test.
UNASSIGNED: A total of 117 patients aged 71.4±4.7 years were included in the study. The telemonitoring intervention incurred an annual infrastructure costs of €489.4 and operational costs of €97.3 (95% CI 85.7-109.0) per patient. Patient annual participation costs were €215.6 (95% CI 190.9-241.1). Average annual out-of-pocket costs for both groups were €345 (95% CI 221-469). After 12 months the telemonitoring group reported significantly lower out-of-pocket costs (€132 vs. €545, p<0.001), driven by reduced spending on food, dietary supplements, medical equipment, and specialist check-ups compared to the standard care group.
UNASSIGNED: To optimise the cost structure of telemonitoring, strategies like shortening the telemonitoring period, developing a national telemonitoring platform, using patient devices, integrating artificial intelligence into platforms, and involving nurse practitioners as telemedicine centre coordinators should be explored.
UNASSIGNED: Telemonitoring predstavlja učinkovit pristop za izboljšanje urejenosti bolnikov z arterijsko hipertenzijo (AH) in sladkorno boleznijo (SB) tipa 2, vendar analize stroškovne strukture niso na voljo. Namen raziskave je raziskati stroškovno strukturo telemonitoringa pri starejših bolnikih z AH in SB tipa 2 v primarnem zdravstvenem varstvu in ugotoviti dejavnike, ki vplivajo na stroške za morebitne prihodnje širitve.
UNASSIGNED: S pomočjo pristopa od spodaj navzgor smo ocenili infrastrukturne in operativne stroške, stroške sodelovanja bolnikov in stroške iz žepa. Infrastrukturne stroške smo izračunali tako, da smo stroške nakupa telemedicinske opreme in spletne platforme delili s številom sodelujočih bolnikov. Operativne stroške in stroške sodelovanja bolnikov smo izračunali z upoštevanjem časa za usposabljanje bolnikov, časa za pregled/opravljanje meritev ter časa za telekonzultacije. Spremembe v stroških iz žepa smo ocenili s pomočjo strukturiranega vprašalnika, v katerem so bolniki v obeh skupinah poročali o stroških iz žepa v preteklem letu. Pri statistični analizi smo uporabili t-test za neparne vzorce, Mann-Whitneyev U test in hi-kvadrat test.
UNASSIGNED: V raziskavo je bilo vključenih 117 bolnikov, starih povprečno 71,4 ± 4,7 leta. Letni infrastrukturni stroški telemonitoringa so znašali 489,4 €, operativni stroški pa 97,3 € (95 % interval zaupanja [IZ] 85,7–109,0) na bolnika. Letni stroški sodelovanja bolnikov so znašali 215,6 € (95 % IZ 190,9-241,1). Povprečni letni stroški iz žepa za obe skupini so znašali 345 € (95 % IZ 221-469). Po 12 mesecih je skupina s telemonitoringom poročala o bistveno nižjih stroških iz žepa (132 € proti 545 €, p < 0,001), pri čemer so se pomembno zmanjšali stroški za hrano in prehranska dopolnila, medicinsko opremo in samoplačniške specialistične preglede.
UNASSIGNED: Za optimizacijo stroškovne strukture telemonitoringa je potrebno preučiti strategije, kot so skrajšanje obdobja telemonitoringa po stabilizaciji kliničnih parametrov, razvoj nacionalne platforme za spremljanje na daljavo z možnostjo prenosa mobilne aplikacije na osebne naprave bolnikov, vključevanje umetne inteligence v spletne platforme in povečanje vloge diplomirane medicinske sestre na mestu koordinatorja telemedicinskega centra.

Managing investments in dairy cow health at a national and global scale, requires an improved understanding of current on-farm expenses for cow health (e.g., expenditure for medicine and veterinary consultations). The aim of this study was to assess on-farm health investments for typical dairy farms in 15 case study countries, including Argentina, Australia, Bangladesh, Brazil, Canada, India, China, Colombia, Indonesia, Kenya, New Zealand, Uganda, UK, Uruguay, and USA. The study was conducted using a descriptive analysis of a secondary data set that was obtained from the International Farm Comparison Network (IFCN). The results suggest that health expenditures take up a relatively small proportion (<10%) of the annual total production costs per cow across all countries in the sample. The means of production costs (e.g., feed, machinery) can take up to 90% of the total production costs for highly intensive systems, while these costs can be as low as 9% for extensive systems. This study highlights the importance of understanding on-farm animal health investments as a contribution to improved national and global decision making about animal health in the dairy sector.

BACKGROUND: Worldwide, progressive chronic, non-malignant diseases are highly prevalent. Especially with increasing age, they are characterised by high hospitalisation rates and high healthcare costs. Improved interprofessional collaboration between general practitioners (GPs) and specialist palliative home care (SPHC) teams might reduce hospitalisation while improving symptoms and quality of life, or preventing them from deterioration. The aim of this study was to examine the cost-effectiveness of a newly developed intervention in patients with advanced chronic, non-malignant diseases consisting of a structured palliative care nurse-patient consultation followed by an interprofessional telephone case conference.
METHODS: The analysis was based on data from 172 participants of the KOPAL multi-centre, cluster randomised controlled trial. Patients with advanced congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), or dementia were randomised into intervention group (IG) and control group (CG, usual care). Cost-effectiveness was examined over 48 weeks from a societal and healthcare payer\'s perspective. Effects were quantified as quality-adjusted life years (QALYs, EQ-5D-5L). Incremental cost-effectiveness ratios were calculated and cost-effectiveness acceptability curves were constructed.
RESULTS: Baseline imbalances in costs and effects could be observed between IG and CG. After adjusting for these imbalances and compared to the CG, mean costs in the IG were non-significantly higher from a societal and lower from a payer\'s perspective. On the effect side, the IG had marginally lower mean QALYs. The results were characterized by high statistical uncertainty, indicated by large confidence intervals for the cost and effect differences between groups and probabilities of cost-effectiveness between 18% and 65%, depending on the perspective and willingness-to-pay.
CONCLUSIONS: Based on the results of this study, the cost-effectiveness of the KOPAL intervention was uncertain. The results highlighted (methodological) challenges of economic evaluations in patients with chronic, non-malignant diseases related to sample size, heterogeneity of participants, and the way the intervention effectiveness is typically captured in economic evaluations.

Background: There are concerns with inappropriate prescribing of antibiotics in hospitals especially broad spectrum in Pakistan and the subsequent impact on antimicrobial resistance rates. One recognized way to reduce inappropriate prescribing is for empiric therapy to be adjusted according to the result of culture sensitivity reports. Objective: Using culture sensitivity reports to optimize antibiotic prescribing in a teaching hospital in Pakistan. Methods: A retrospective observational study was undertaken in Ghurki Trust Teaching Hospital. A total of 465 positive cultures were taken from patients during the study period (May 2018 and December 2018). The results of pathogen identification and susceptibility testing from patient-infected sites were assessed. Additional data was collected from the patient\'s medical file. This included demographic data, sample type, causative microbe, antimicrobial treatment, and whether empiric or definitive treatment as well as medicine costs. Antimicrobial data was assessed using World Health Organization\'s Defined Daily Dose methodology. Results: A total of 497 isolates were detected from the 465 patient samples as 32 patients had polymicrobes, which included 309 g-negative rods and 188 g-positive cocci. Out of 497 isolates, the most common Gram-positive pathogen isolated was Staphylococcus aureus (Methicillin-sensitive Staphylococcus aureus) (125) (25.1%) and the most common Gram-negative pathogen was Escherichia coli (140) (28.1%). Most of the gram-negative isolates were found to be resistant to ampicillin and co-amoxiclav. Most of the Acinetobacter baumannii isolates were resistant to carbapenems. Gram-positive bacteria showed the maximum sensitivity to linezolid and vancomycin. The most widely used antibiotics for empiric therapy were cefoperazone plus sulbactam, ceftriaxone, amikacin, vancomycin, and metronidazole whereas high use of linezolid, clindamycin, meropenem, and piperacillin + tazobactam was seen in definitive treatment. Empiric therapy was adjusted in 220 (71.1%) cases of Gram-negative infections and 134 (71.2%) cases of Gram-positive infections. Compared with empiric therapy, there was a 13.8% reduction in the number of antibiotics in definitive treatment. The average cost of antibiotics in definitive treatment was less than seen with empiric treatment (8.2%) and the length of hospitalization also decreased. Conclusions: Culture sensitivity reports helped reduced antibiotic utilization and costs as well as helped select the most appropriate treatment. We also found an urgent need for implementing antimicrobial stewardship programs in hospitals and the development of hospital antibiotic guidelines to reduce unnecessary prescribing of broad-spectrum antibiotics.

The inhibition of cytochrome P450 (CYP) enzymes is the most frequent cause of drug-drug interactions. Many safe, inexpensive and widely available therapeutic drugs can inhibit CYP enzymes (e.g., azoles). Also, the specific potency of inhibition and the targeted CYP enzyme have been well described (e.g., itraconazole strongly inhibits CYP enzyme 3A4 and, in turn, CYP3A4 metabolizes venetoclax and ibrutinib). CYP enzyme inhibitors increase the plasma concentration of other drugs via shared metabolic pathways. We herein present the effects of inhibiting CYP enzymes with itraconazole-venetoclax for the treatment of refractory acute myeloid leukaemia, as well as itraconazole-ibrutinib to treat steroid-refractory acute graft vs. host disease in the same patient. Both of the patient\'s conditions responded completely. This appears to be a feasible strategy that decreases treatment costs by 75%. Previous Food and Drug Administration recommendations and clinical data support these subsequent dose reductions. Eleven months after the transplant, the patient remains in complete response and with no minimal residual disease. Another patient had been effectively treated before with CYP enzyme inhibition prior to venetoclax-itraconazole administration for orbital myeloid sarcoma. Thus, this case study furthers information on the CYP enzyme inhibition strategy when associated with another costly drug, ibrutinib. The CYP enzyme inhibition strategy could be applied to many more anticancer drugs (e.g., ruxolitinib and ponatinib) and facilitate the availability of expensive oncological treatments in low- and middle-income countries. Also, this strategy could be further generalized by using different CYP enzyme inhibitors with varied pharmacokinetic and pharmacodynamic properties (i.e., grapefruit, azoles and clarithromycin).

BACKGROUND: There are multiple treatments for a chronic subdural hematoma, a significant cause of neurosurgical morbidity that cost the healthcare system $5B in 2007, but few generalizable prospective studies. The purpose of this study was to examine outcomes of bedside Subdural Evacuation Port System (SEPS) placement as compared to operating room burr hole evacuation (BHE) to acquire data to support a randomized trial.
METHODS: All procedures were performed in a single institution between 2011 and 2019. Patients were included if > 18 years of age, had chronic subdural hematoma, and were treated by SEPS or BHE. Patients with prior neurosurgical history, mass lesions or bilateral hematomas were excluded. Patients who met inclusion for SEPS (n = 55) or BHE (n = 105). Samples were propensity matched to account for variability. Non-inferiority tests compared outcomes. Cost data was obtained through billable charges.
RESULTS: Patients with multiple comorbidities were more likely to undergo SEPS drainage. Noninferiority tests reported no statistically significant evidence to suggest SEPS drains were worse in reoperation-rate (18% vs 9%), post-operative seizure, or functional outcome. SEPS drain placement trended towards a faster time to procedure (3 h faster; p = 0.07) but the overall hospital stay was longer (4.23 vs 5.81, p = 0.01). SEPS drain placement costs are less than BHE, but these patients had 25% higher overall hospital costs (p = 0.01) due to comorbidities and increased hospital stay.

BACKGROUND: Good patient access to medicines at home during the last 12 months of life is critical for effective symptom control, prevention of distress and avoidance of unscheduled and urgent care.
OBJECTIVE: To undertake an evaluation of patient and carer access to medicines at end-of-life within the context of models of service delivery.
METHODS: Evaluative, mixed method case studies of service delivery models, including cost analysis. The unit of analysis was the service delivery model, with embedded sub-units of analysis.
METHODS: (i) General Practitioner services (ii) Palliative care clinical nurse specialist prescribers (iii) a 24/7 palliative care telephone support line service.
METHODS: Healthcare professionals delivering end-of-life care; patients living at home, in the last 12 months of life, and their carers.
METHODS: Within each case: Patients/carers completed a structured log on medicines access experiences over an 8-week period. Logs were used as an aide memoire to sequential, semi-structured interviews with patients/carers at study entry, and at four and eight weeks. Healthcare professionals took part in semi-structured interviews focused on their experiences of facilitating access to medicines, including barriers, and facilitating factors. Data on prescribed medicines were extracted from patient records. Detailed contextual data on each case were also collected from a range of documents. Patient, carer and healthcare professional interview data were analysed using Framework Analysis to identify main themes. We estimated prescription costs and budget impact analysis of the different service models. Data were triangulated within each case. Cross-case comparison and logic models were employed to enable systematic comparisons across service delivery types.
RESULTS: Accessing medicines is a process characterised by complexity and systems inter-dependency requiring considerable co-ordination work by patients, carers and healthcare professionals. Case studies highlighted differences in speed and ease of access to medicines across service delivery models. Key issues were diversifying the prescriber workforce, the importance of continuity of relationships and team integration, access to electronic prescribing systems, shared records and improved community pharmacy stock. Per patient prescription cost differentials between services were modest but were substantial when accounting for the eligible population over the medium term.
CONCLUSIONS: Experiences of medicines access would be improved through increasing numbers of nurse and pharmacist prescribers, and improving shared inter-professional access to electronic prescribing systems and patient records, within care delivery systems that prioritise continuity of relationships. Community pharmacy stock of palliative care medicines also needs to become more reliable.