Purpose Early diagnosis and treatment of leprosy and leprosy reactions are essential to prevent stigmatizing deformities and disability. Although the incidence of leprosy has decreased enormously, grade 2 disability due to nerve injury has remained the same. New tools are needed to better diagnose and monitor leprosy reactions and associated neuritis and this study assessed whether high-resolution sonography (HRUS) can be used as such a tool. Materials and Methods During a prospective follow-up period of 2 years at regular intervals, we performed clinical examination to assess sensory and motor function and HRUS of the four main peripheral nerves in 57 patients, of whom 36 were with reactions and 21 were without reactions. Normative data of the cross-sectional area (CSA) of these nerves were obtained from 55 healthy subjects (HS). Color Doppler (CD) was used to study blood flow in the nerves. Results At the baseline visit and during follow-up, all four nerves were significantly thicker in patients with leprosy reactions in comparison to HS (p < 0.0001) and to a lesser extent also in comparison to patients without reactions ranging from a p-value of < 0.05 to < 0.0001 in the different nerves tested. During follow-up, the nerve size did not change significantly in patients without reactions, while it decreased significantly in patients with reactions. At baseline, endoneural blood flow was present only in patients with reactions. This occurred in 20 of the 36 (55 %) patients (49 nerves) and decreased to only 1 patient (2.7 %) at the end of the follow-up period. Conclusion This prospective study demonstrates the ability of HRUS to monitor disease activity and the effect of treatment in patients with leprosy reactions by determining changes in nerve size and vascularity, which are indicators of peripheral nerve involvement and damage. Ziel Frühe Diagnose und Therapie der Lepra und der Lepra-Reaktionen ist entscheidend, um stigmatisierende Entstellungen und Behinderungen zu verhindern. Obwohl die Lepra-Inzidenz immens gesunken ist, ist eine Behinderung 2. Grades aufgrund der Nervenschädigung gleich häufig geblieben. Neue Verfahren für eine bessere Diagnose und Überwachung der Lepra-Reaktionen und der assoziierten Neuritis sind erforderlich, daher überprüft diese Studie, ob HRUS hierfür eingesetzt werden kann. Material und Methoden Während eines prospektiven Nachuntersuchungszeitraums von 2 Jahren mit gleichmäßigen Intervallen führten wir bei 57 Patienten eine klinische Untersuchung der sensorischen und motorischen Funktionen und HRUS der vier peripheren Hauptnerven durch, von denen 36 Reaktionen und 21 keine Reaktionen zeigten. Die normativen Werte der Querschnittsregion (CSA) dieser Nerven wurden bei 55 Gesunden erhoben. Farbdopplersonografie wurde durchgeführt, um den Blutfluss in den Nerven zu ermitteln. Ergebnisse: Beim Erstbesuch und während der Folgeuntersuchungen waren bei allen Patienten mit Lepra-Reaktionen im Vergleich zu gesunden alle vier Nerven signifikant dicker (p < 0,0001) und in geringerem Maße auch im Vergleich zu Patienten ohne Reaktionen, die in einem p-Wert-Bereich zwischen < 0,05 und < 0,0001 für die verschiedenen untersuchten Nerven lagen. Während der Folgeuntersuchungen veränderte sich bei Patienten ohne Reaktion die Größe der Nerven kaum, während sie bei Patienten mit Reaktionen signifikant kleiner wurden. Bei Erstaufnahme war der endoneurale Blutfluss nur bei Patienten mit Reaktionen vorhanden, dies traf für 20 (55 %) der 36 Patienten zu (49 Nerven) und sank auf nur einen Patienten (2,7 %) am Ende des Nachsorgezeitraums ab. Schlussfolgerung Diese prospektive Studie zeigt die Möglichkeit des HRUS, die Erkrankungsaktivität und den Therapieerfolg bei Patienten mit Lepra-Reaktionen zu überwachen, indem die Veränderungen der Nervengröße und Durchblutung bestimmt werden, welche Hinweise auf eine Beteilung der peripheren Nerven und deren Schädigung geben.

Corticosteroids have been extensively used in the treatment of immunological reactions and neuritis in leprosy. The present study evaluates the serological response to steroid treatment in leprosy reactions and neuritis. Seven serological markers [TNF-α, antibodies to Phenolic glycolipid-1 (PGL-1 IgM and IgG), Lipoarabinomannan (LAM IgG1 and IgG3), C2-Ceramide and S100 B] were analyzed longitudinally in 72 leprosy patients before, during and after the reaction. At the onset of reaction these patients received a standard course of prednisolone. The levels of the above markers were measured by Enzyme linked immunosorbent assay (ELISA) and compared with the individuals own value in the month prior to the reaction and presented as percentage increase. One month before the reaction individuals showed a varying increase in the level of different markers such as TNF-α (53%) and antibodies to Ceramide (53%), followed by to PGL-1 (51%), S100B (50%) and LAM (26%). The increase was significantly associated with clinical finding of nerve pain, tenderness and new nerve function impairment. After one month prednisolone therapy, there was a fall in the levels [TNF-α (60%), C2-Ceramide (54%), S100B (67%), PGL-1(47%) and LAM (52%)] with each marker responding differently to steroid. Reactions in leprosy are inflammatory processes wherein a rise in set of serological markers can be detected a month before the clinical onset of reaction, some of which remain elevated during their action and steroid treatment induces a variable fall in the levels, and this forms the basis for a variable individual response to steroid therapy.

Summary: Sickle cell disease (SCD) with vaso‐occlusive pain crisis (VOC) significantly impacts patient well‐being and often results in extensive healthcare resource utilization. This study assessed the VOC burden, its management and its impact on patients' quality of life (QoL). A cross‐sectional observational study was conducted between November 2021 and June 2022, including 1000 SCD patients from high‐prevalence states in India. Data on demographics, clinical characteristics, VOC severity, management and QoL were collected. The study revealed that 33.5% of patients reported at least one VOC episode during the study period. In the year prior to their enrolment, 836 (83.60%) patients reported at least one VOC episode, with an equal proportion of 407/487 (83.6%) adults and 429/513 (83.6%) paediatric patients, reducing their QoL across all domains compared to patients without VOC. Of these, 469/1000 patients (46.9%) experienced ≥3 VOC episodes. Additionally, 764/1000 (76.40%) patients managed their VOCs at healthcare facilities, with 501/1000 (50.1%) requiring inpatient admissions. Further, 71.80% of patients received Hydroxyurea (HU) therapy. The study depicts the severity of the Arab–Indian haplotype in Indian SCD patients visiting healthcare settings based on high VOC burden. This highlights the urgent need for better management strategies and resource allocation for these patients.

Journal of Medical Internet Research - International Scientific Journal for Medical Research, Information and Communication on the Internet #Preprint #PeerReviewMe: Warning: This is a unreviewed preprint. Readers are warned that the document has not been peer-reviewed by expert/patient reviewers or an academic editor, may contain misleading claims, and is likely to undergo changes before final publication, if accepted, or may have been rejected/withdrawn. Readers with interest and expertise are encouraged to sign up as peer-reviewer, if the paper is within an open peer-review period. Please cite this preprint only for review purposes or for grant applications and CVs (if you are the author). Background: Successful models of information and communication technology (ICT) applied to cost-effective delivery of quality care in low- and middle-income countries (LMIC) are an increasing necessity. Severe thalassemia (ST) is one of the most common life-threatening non-communicable diseases of children globally. Objective: To study the impact of ICT on quality of care for ST patients in LMIC. Methods: A total of 1110 patients with ST from 5 centers in India were followed over a one-year period. The impact of consistent use of a web-based application platform designed to assist comprehensive management of ST (ThalcareTM) on key indicators of quality of care such as minimum (pre-transfusion) hemoglobin, serum ferritin, liver size and spleen size was assessed. Results: For four centers, the improvement in mean pre-transfusion hemoglobin level was statistically very significant (P<0.001). Four out of five centers achieved reduction in mean ferritin levels with two displaying a highly significant drop in ferritin (P=0.003 and P=0.0002). One of the five centers did not record liver and spleen size on palpation, but out of the remaining 4 centers, 2 witnessed a strongly significant drop in liver and spleen size (P <0.01), 1 witnessed moderate drop (P= 0.05 for liver P =0.03 for spleen size) while the fourth witnessed a moderately increase in liver size (P =0.08) and insignificant change in spleen size (P=0.12). Conclusions: Implementation of Computer-Assisted Treatment Planning and Performance Assessment positively impacted on indices reflecting effective delivery of care to patients suffering from ST in LMIC consistently.

Sickle cell disease (SCD) is the most prevalent life-threatening blood monogenic disorder. Currently, there is no cure available, apart from bone marrow transplantation. Early and efficient diagnosis of SCD is key to disease management, which would make considerable strides in alleviating morbidity and reducing mortality. However, the cost and complexity of diagnostic procedures, such as the Sanger sequencing method, impede the early detection of SCD in a resource-limited setting. To address this, the current study demonstrates a simple and efficient proof-of-concept assay for the detection of patients and carriers using extraction-free non-invasive buccal swab samples by isothermal DNA Amplification coupled Restrictase-mediated cleavage (iDAR). This study is a first of its kind reporting the use of buccal swab specimens for iDA in molecular diagnosis of a genetic disease, all the while being cost effective and time saving, with the total assay time of around 150 min at a cost of USD 5. Further, iDAR demonstrates 91.5% sensitivity and 100% specificity for detecting all three alleles: SS, AS, and AA, having a 100% concordance with Sanger sequencing. The applicability of the iDAR assay is further demonstrated with its adaptation to a one-pot reaction format, which simplifies the assay system. Overall, iDAR is a simple, cost-effective, precise, and non-invasive assay for SCD screening, with the potential for use in a limited resource setting.