Timeliness, efficiency and public procurement in hip surgery in Italy

Considering different perspectives, the scope of this thesis is to investigate how to improve healthcare resources allocation and the provision efficiency for hip surgeries, a resource-intensive operation, among the most frequently performed on the elderly, with a trend in volume that is increasing in years due to population aging. Firstly, the effect of Time-To-Surgery (TTS) on mortality for hip fracture patients is investigated. The analysis attempts to account for TTS endogeneity due to the inability to fully control for variables affecting patient delay – e.g. patient severity. Exploiting an instrumental variable model, where being admitted on Friday or Saturday predicts longer TTS, findings show exogenous TTS does not have a significant effect on mortality. Thus suggesting surgeons prioritize patients effectively, neutralizing the adverse impact of longer TTS. Then, the volume-outcome relation for total hip replacement surgery is analyzed, seeking to account for selective referral, which may be present in elective surgery context, and induce reverse causality issue in the volume-outcome relation. The analysis employs a conditional choice model where patient travel distance from all regions' hospitals is used as a hospital choice predictor. Findings show the exogenous hospital volume significantly decreases adverse outcomes probability, especially in the short run. Finally, the change in public procurement design enforced in the Romagna LHA (Italy) is exploited to assess its impact on hip prostheses cost, surgeons' implant choice, and patient health outcomes. Hip prostheses are the major cost-driver of hip replacement surgeries, hence it is crucial to design the public tender such that implant prices are minimized, but cost-containment policies have to be weighted with patient well-being. Evidence shows that a cost reduction occurred without a significant surgeons’ choices impact. Positive or no effect of surgeons specialization is found on patients outcomes after the new procurement introduction.

Aragonite-based scaffold for the treatment of knee osteochondral defects: results of a prospective multi-center trial at 2 years' follow-up

PURPOSE: To evaluate the clinical and MRI outcomes after the implantation of a nanostructured cell free aragonite-based scaffold in patients affected by knee chondral and osteochondral lesions. METHODS: 126 patients (94 men, 32 women; age 32.7±8.8 years) were included according to the following criteria: grade III or IV chondra/osteochondral lesions in the femoral condyles or throclea; 2) no limb axial deviation (i.e. varus or valgus knee > 5°); 3) no signs of knee instability; 4) no concurrent tibial or patellar chondral/osteochondral defects. All patients were treated by arthrotomic implantation of an aragonite based-scaffold by a press-fit technique. Patients were prospectively evaluated by IKDC, Tegner, Lysholm and KOOS scores preoperatively and then at 6, 12, 18 and 24-months follow-up. MRI was also performed to evaluate the amount of defect filling by regenerated cartilage. Failures were defined as the need for re-intervention in the index knee within the follow-up period. RESULTS: Average defect size was 2±1.3 cm2 and in most cases a single scaffold was used. A significant improvement in each clinical score was recorded from basal level to 24 months’ follow-up. In particular, the IKDC subjective score increased from 42.14±16 to 70.94±24.69 and the Tegner score improved from 2.95±1.90 to 4.82±1.85 (p<0.0005). Lysholm score and all the subscales of KOOS showed a similar trend over time. Age of the patient at implantation, size of the defect and BMI were correlated with lower clinical outcome. The presence of OA didn’t influence the clinical results. MRI evaluation showed a significant increase in defect filling over time, with the highest value reached at 24 months. Failures occurred in eleven patients (8.7%). CONCLUSION: The aragonite-based biomimetic osteochondral scaffold proved to be safe, and encouraging clinical and radiographic outcomes were documented up to 2 years’ follow-up.

Role of gender in transthyretin-related amyloidosis: an international perspective based on the Transthyretin Amyloid Outcomes Survey (THAOS)

Background. Transthyretin amyloidosis (ATTR) is an underdiagnosed disease caused by destabilization of transthyretin (TTR) due to pathogenic mutations (ATTRm) or aging (ATTRwt). We explored the role of gender in determining clinical picture using the largest available database on ATTR, the ongoing Transthyretin Amyloid Outcomes Survey (THAOS) international registry. Methods. Data through 1st April 2019 were explored. Symptomatic ATTRm (n=3737), asymptomatic ATTRm (n=644) and ATTRwt (n=874) patients were studied. Results. Male prevalence was 61% in the entire registry, 53% in ATTRm and 95% in ATTRwt. In the overall cohort, cardiac phenotype was more frequent in males (30.7% vs 10.5%, p<0.001). Among ATTRm, 72.3% of patients with amyloidotic cardiomyopathy (ATTR-CM) were males (p<0.001) but echocardiographic features showed no substantial gender differences. Sensory abnormalities (70.1% vs 64.1%, p<0.001), autonomic abnormalities (60% vs 48.5%, p<0.001) and walking disabilities were more frequent among ATTRm males. Carpal tunnel syndrome was more frequent in ATTRm males (18.6% vs 15.5%, p=0.014). In ATTRwt cohort, females had a more pronounced (but anyhow mild) walking disability. Male-to-female ratio varied within genotype, from 0.61 in Val30Met to 11.11 in ATTRwt; furthermore, males’ imbalance was more evident among symptomatic patients rather than in asymptomatic ones. Male gender, age at presentation and specific genotype were independently associated with the presence of ATTR-CM. Conclusions. In ATTR, cardiac involvement is more frequent in men, supporting the hypothesis that some biologic characteristics may “protect” from myocardial amyloid infiltration in women. Further investigations are needed to identify possible underlying protective mechanism and orient the research for innovative, gender-tailored therapeutic approaches.