Musculoskeletal manifestations associated with transthyretin-mediated (ATTR) amyloidosis: a systematic review.

BACKGROUND: Hereditary and wild-type transthyretin-mediated (ATTRv and ATTRwt) amyloidoses result from the misfolding of transthyretin and aggregation of amyloid plaques in multiple organ systems. Diagnosis of ATTR amyloidosis is often delayed due to its heterogenous and non-specific presentation. This review investigates the association of musculoskeletal (MSK) manifestations with ATTR amyloidosis and the delay from the onset of these manifestations to the diagnosis of ATTR amyloidosis. METHODS: This systematic review utilized Medline and EMBASE databases. Search criteria were outlined using a pre-specified patient, intervention, comparator, outcome, time, study (PICOTS) criteria and included: amyloidosis, ATTR, and MSK manifestations. Publication quality was assessed utilizing Joanna Briggs Institute (JBI) critical appraisal checklists. The search initially identified 7,139 publications, 164 of which were included. PICOTS criteria led to the inclusion of epidemiology, clinical burden and practice, pathophysiology, and temporality of MSK manifestations associated with ATTR amyloidosis. 163 publications reported on ATTR amyloidosis and MSK manifestations, and 13 publications reported on the delay in ATTR amyloidosis diagnosis following the onset of MSK manifestations. RESULTS: The MSK manifestation most frequently associated with ATTR amyloidosis was carpal tunnel syndrome (CTS); spinal stenosis (SS) and osteoarthritis (OA), among others, were also identified. The exact prevalence of different MSK manifestations in patients with ATTR amyloidosis remains unclear, as a broad range of prevalence estimates were reported. Moreover, the reported prevalence of MSK manifestations showed no clear trend or distinction in association between ATTRv and ATTRwt amyloidosis. MSK manifestations precede the diagnosis of ATTR amyloidosis by years, and there was substantial variation in the reported delay to ATTR amyloidosis diagnosis. Reports do suggest a longer diagnostic delay in patients with ATTRv amyloidosis, with 2 to 12 years delay in ATTRv versus 1.3 to 1.9 years delay in ATTRwt amyloidosis. CONCLUSION: These findings suggest that orthopedic surgeons may play a role in the early diagnosis of and treatment referrals for ATTR amyloidosis. Detection of MSK manifestations may enable earlier diagnosis and administration of effective treatments before disease progression occurs.

Economic and humanistic burden of HPV-related disease in Indonesia: A qualitative analysis.

The burden of human papillomavirus (HPV) and HPV-related cancers and genital warts is increasing in developing countries, including Indonesia. The objective of this study was to qualitatively explore the humanistic and economic burden of these HPV-related diseases in patients in Indonesia. In 2021, in-depth interviews and focus groups were conducted with patients (N = 18) with HPV-related diseases and healthcare professionals (HCPs; N = 10) specialised in treating these patients. Interviews explored the physical, mental, social, and economic burden of HPV-related diseases. Patients emphasised the psychological and social burden of HPV-related diseases, which negatively impacted their mental state and close relationships. Treatment for HPV-related diseases was also associated with a substantial cost, which health insurance only partially alleviated. HCPs understood the physical negative impact of HPV-related diseases, but some understated patients' social, psychological, and financial burden. This research underscores the substantial economic and humanistic burden of HPV-related diseases that could be prevented by vaccination. In addition, it highlights the need for novel interventions to reduce negative psychosocial consequences of HPV-related diseases in Indonesia. Increased HCP education of the broader humanistic impacts of HPV-related diseases may improve patient support and increase awareness for preventive strategy.

Expert Consensus on Real-World Use and Consumption Patterns of a Fixed-Dose Combination Foam for Psoriasis as a Reactive Management (RM) and Proactive Management (PAM) Regimen.

INTRODUCTION: Plaque psoriasis is a chronic skin disease characterised by periods of remission and relapse and associated with considerable burden to patients and healthcare systems. For most patients, standard-of-care is reactive management (RM) with topical therapies, but, more recently, the benefits of proactive management (PAM) have been recognised. This study aimed to gain consensus on real-world use and consumption in RM versus PAM regimens, based on fixed-dose combination calcipotriol and betamethasone dipropionate (Cal/BD) foam which, following a recent update, is currently the only topical therapy for psoriasis with a long-term maintenance regimen in its label. METHODS: The modified-Delphi approach was used to gain insights and consensus on real-world views, use and consumption in RM versus PAM from a panel of dermatologists with experience prescribing Cal/BD foam as PAM. The panel included 16 dermatologists, 4 each from France, Germany, Italy, and Spain, and included two questionnaire rounds and a meeting to obtain final consensus. RESULTS: The panel agreed that topicals are burdensome to apply in clinical practice and that poor patient adherence, particularly long-term, is a barrier to effective psoriasis management. The panel advised that, as they prescribe a similar number of cans for RM and PAM over a given period, consumption is not a key driver influencing future decisions to prescribe PAM, even in instances where prescribing differences could be observed. Instead, the panel agreed that patient- and disease-related factors better determine patient suitability for PAM. CONCLUSION: This modified-Delphi study confirms that prescription of RM or PAM, with Cal/BD foam, is largely driven by patient-related factors and patient involvement is key to optimise outcomes. Real-world experiences captured in this study suggest that a PAM regimen does not increase overall consumption, and thus costs per patient for payers and prescribers, in comparison to RM.