Long-term antibiotic prophylaxis for prevention of rheumatic fever recurrence and progression to rheumatic heart disease.

BACKGROUND: Rheumatic fever is a non-suppurative, inflammatory sequela of group A Streptococcus pharyngitis that can occur at two to four weeks after infection. Following an episode of rheumatic fever, there is a risk of developing rheumatic heart disease (RHD) later in life that carries significant risk of morbidity and mortality. RHD remains the largest global cause of cardiovascular disease in the young (age < 25 years). The historical literature provides inconclusive evidence that antibiotic prophylaxis is beneficial in reducing the risk of recurrence of rheumatic fever and development of RHD. Antibiotics are thought to work by reducing the carriage of group A Streptococcus and thus reducing the risk of infection. This review was commissioned by the World Health Organization (WHO) for an upcoming guideline. OBJECTIVES: 1. To assess the effects of long-term antibiotics versus no antibiotics (control) for secondary prevention of rheumatic fever recurrence and associated sequelae in people with previous rheumatic fever or RHD. 2. To assess the effects of long-term intramuscular penicillin versus long-term oral antibiotics for secondary prevention of rheumatic fever recurrence and associated sequelae in people with previous rheumatic fever or RHD. SEARCH METHODS: We systematically searched CENTRAL, MEDLINE, Embase, Conference Proceedings Citation Index-Science, clinical trial registers, ISRCTN.com and reference lists without restrictions on language or date up to 10 March 2024. SELECTION CRITERIA: We sought randomised controlled trials or quasi-randomised trials, described in any language, including participants with previous rheumatic fever and/or RHD of any age, based in community or hospital settings. Studies were included if they compared firstly antibiotic prophylaxis with no antibiotic prophylaxis, and, secondly, intramuscular penicillin prophylaxis versus oral antibiotic prophylaxis. DATA COLLECTION AND ANALYSIS: We used standardised methodological, Cochrane-endorsed procedures and performed meta-analyses with risk ratios (RR) and Peto odds ratios (Peto OR). Our primary outcomes were recurrence of rheumatic fever, progression or severity of RHD and cardiac complications. Our secondary outcomes were obstetric complications (maternal and foetal events), mortality, treatment adherence, adverse events and acceptability to participants. We performed comprehensive assessments of risk of bias and certainty of evidence, applying the GRADE methodology. MAIN RESULTS: We included 11 studies (seven RCTs and four quasi-randomised trials) including 3951 participants. The majority of the included studies were conducted in the USA, UK and Canada during the 1950s to 1960s. Most participants with previous rheumatic fever had been diagnosed using the modified Jones criteria (mJC) (four studies), were an average of 12.3 years of age and 50.6% male. We assessed the majority of the included studies to be at high risk of bias, predominantly relating to blinding and attrition bias. Comparison one: antibiotics versus no antibiotics Pooled meta-analysis of six RCTs provides moderate-certainty evidence that antibiotics overall (oral or intramuscular) probably reduce the risk of recurrence of rheumatic fever substantially (0.7% versus 1.7%, respectively) (risk ratio (RR) 0.39, 95% confidence interval (CI) 0.22 to 0.69; 1721 participants). People with early or mild RHD likely have the greatest capacity to benefit from intramuscular antibiotic prophylaxis (8.1%) compared to no antibiotics (0.7%) (RR 0.09, 95% CI 0.03 to 0.29; 1 study, 818 participants; moderate-certainty evidence). Antibiotics may not affect mortality in people with late-stage RHD (RR 1.23, 95% CI 0.78 to 1.94; 1 study, 994 participants; low-certainty evidence). Antibiotics may not affect the risk of anaphylaxis (Peto odds ratio (OR) 7.39, 95% CI 0.15 to 372; 1 study, 818 participants; low-certainty evidence) or sciatic nerve injury (Peto OR 7.39, 95% CI 0.15 to 372; 1 study, 818 participants; low-certainty evidence) compared with no antibiotics, but probably have an increased risk of hypersensitivity reactions (RR 137, 8.51 to 2210; 2 studies, 894 participants; moderate-certainty evidence) and local reactions (RR 29, 1.74 to 485; 1 study, 818 participants; moderate-certainty evidence). Comparison two: intramuscular antibiotics versus oral antibiotics Pooled analysis of two RCTs showed that prophylactic intramuscular benzathine benzylpenicillin likely reduces recurrence of rheumatic fever substantially when compared to oral antibiotics (0.1% versus 1%, respectively) (RR 0.07, 95% CI 0.02 to 0.26; 395 participants; moderate-certainty evidence). Furthermore, it is unclear whether intramuscular benzyl penicillin is superior to oral antibiotics in reducing the risk of mortality in the context of RHD (Peto OR 0.22, 95% CI 0.01 to 4.12; 1 study, 431 participants; very low-certainty evidence). There were no data available on progression of latent RHD or adverse events including anaphylaxis, sciatic nerve injury, delayed hypersensitivity/allergic reactions and local reactions to injection. AUTHORS' CONCLUSIONS: This review provides evidence that antibiotic prophylaxis likely reduces the risk of recurrence of rheumatic fever compared to no antibiotics, and that intramuscular benzathine benzylpenicillin is probably superior to oral antibiotics (approximately 10 times better). Moreover, intramuscular benzathine benzylpenicillin likely reduces the risk of progression of latent RHD. Evidence is scarce, but antibiotics compared with no antibiotics may not affect the risk of anaphylaxis or sciatic nerve injury, but probably carry an increased risk of hypersensitivity reactions and local reactions. Antibiotics may not affect all-cause mortality in late-stage RHD compared to no antibiotics. There is no evidence available to comment on the effect of intramuscular penicillin over oral antibiotics for progression of latent RHD and adverse events, and little evidence for all-cause mortality. It is important to interpret these findings in the context of major limitations, including the following: the vast majority of the included studies were conducted more than 50 years ago, many before contemporary echocardiographic studies; methodology was often at high risk of bias; outdated treatments were used; only one study was in latent RHD; and there are concerns regarding generalisability to low socioeconomic regions. This underlines the need for ongoing research to understand who benefits most from prophylaxis.

Candida Tropicalis Endocarditis: A case report and literature review.

Fungi rarely cause infective endocarditis but when they do, they are often associated with poor outcomes. Candida tropicalis accounts for only 10% of Candida endocarditis cases. A case of a 30-year-old male with a history of intravenous drug abuse was reported to the emergency department in August, 2021 with right-sided leg pain and fever for 3 days. A trans-thoracic echocardiogram showed a vegetation on the aortic valve and a computed tomography angiogram showed complete nonopacification of the right-sided common iliac artery and the superficial femoral artery just distal to its branching of the right profunda femoris artery. An emergent right iliofemoral embolectomy was done. Candida tropicalis was isolated from tissue and blood cultures. The patient was successfully treated with aortic valve replacement and intravenous caspofungin. The other reported cases of Candida tropicalis were reviewed and findings were compared with those reported in patients with Candida albicans and Candida parapsilosis endocarditis.

Adult-onset chronic recurrent multifocal osteomyelitis: A case report of a rare entity.

Background: Chronic recurrent multifocal osteomyelitis is a rare autoimmune disorder causing inflammatory joint lesions. It has an estimated prevalence of 1-2 per million while adult-onset disease constitutes only 6.3% of patients. Case report: We present a case of a 44 years old male who presented to the rheumatology clinic with lower back pain for twelve years. Magnetic resonance imaging of the lumbosacral spine showed ovoid areas of abnormal signal intensities along superior and inferior endplates of multiple vertebrae of the dorsolumbar and sacral spine. Computed tomography guided biopsy of L4 vertebrae was done. Histopathology revealed linear cores of degenerating fibrocartilage focally exhibiting small spicules of mineralized bone and fibro-collagenous tissue. He initially did not respond to traditional therapy. His symptoms improved with the addition of a Janus Kinase inhibitor. To the best of our knowledge, this is the first case of chronic recurrent multifocal osteomyelitis to be reported from Pakistan.

COVID-19 and thrombotic thrombocytopenic purpura: A case report.

The clinical presentation of COVID-19 varies from being asymptomatic to developing acute respiratory distress syndrome and multi-organ dysfunction. The diffuse microvascular thrombi in multiple organs seen in the autopsy of COVID-19 patients are similar to that of thrombotic microangiopathy (TMA). TMA is characterised by thrombus formation in the microvasculature with laboratory findings of microangiopathic haemolytic anaemia (MAHA) and thrombocytopenia. A 49-year-old male presented to the Aga Khan University Hospital, Karachi. with fever, diarrhoea, altered level of consciousness, and a positive nasopharyngeal swab for SARS-CoV-2. He developed severe thrombocytopenia, MAHA with 5.8% schistocytes, and worsening renal function on the sixth day of admission. Diagnosis of thrombotic thrombocytopenic purpura (TTP) was established based on PLASMIC score, and he was successfully treated with intravenous (IV) Methylprednisolone, therapeutic plasma exchange and IV Rituximab. The case emphasises the need to keep TTP in the differential diagnosis when a patient with COVID-19 develops severe thrombocytopenia, acute renal failure, or impaired level of consciousness, since prompt diagnosis and treatment is necessary to gain favourable outcome.

Low performance of internal medicine senior residents in in-service examinations.

We observed an unprecedented and consistent low performance of senior residents as compared with juniors in monthly examinations. This compelled us to evaluate systematically and compare the scores of senior residents with their junior colleagues. This retrospective observational study was conducted in April 2020 among internal medicine residents. Residents in first and second year of their training were labelled as junior residents. Residents in third or fourth year of their training were labelled as senior residents. Comparison of mean scores of each resident level was done separately both for monthly formative multiple-choice questions tests, and summative yearly end of term examinations. We discussed the possible reasons as well. There were 67 residents in year 2018 and 69 in 2019. There is no significant difference between scores of monthly examinations of years 2018 and 2019 among residents of each level. Rather, in March and December 2018, junior residents perform better than senior residents with p values of 0.01 and 0.04, respectively. In February and September 2019, senior residents performed better than junior residents with p value of 0.02. Similarly, there is no significant difference in scores of residents of each level in end-of-term examinations of years 2018 and 2019 with p values 0.18 and 0.25, respectively. Performance of senior residents in our residency programme in in-service examinations is relatively low as compared with their junior colleagues. There is a need to evaluate reasons for this relatively low performance of senior residents.

A simple discharge criteria for transfer of patients from intermediate care to general care: a prospective observational study.

OBJECTIVE: To develop and apply a simple criterion for transfer of patients from intermediate care to general care. METHODS: The prospective study was conducted in the intermediate care units of Aga Khan University Hospital, Karachi, from July to December 2018. A discharge criterion for transfer of patients from intermediate care to general care was developed according to which patients with vital signs and Glasgow Coma Scale score within a preset range were considered stable enough for transfer from intermediate care to general care. After labelling the patients on the basis of the criterion, it was determined on the following day which patients remained stable enough for transfer to general care, and which patients became unstable. Data was analysed using SPSS 19. RESULTS: Of the 49 patients with mean age 63.0±16.9 years, 28(57.1%) were males. Overall, 43(87.7%) patients remained stable on the next day. Of them, 33(67.3%) patients were transferred out from intermediate care on the subsequent day, while 8(16.3%) were not transferred out due to primary physician's decision, 1(2%) due to heparin infusion, and 1(2%) due to family request. The condition of the remaining 6(12%) patients deteriorated. CONCLUSIONS: A simple discharge criterion is proposed for intermediate care solely based on clinical.

Compliance of checking HbA1c in a tertiary care hospital of Pakistan.

BACKGROUND AND OBJECTIVES: The prevalence of diabetes mellitus worldwide was 171 million one and half decade ago, while the prediction is 366 million patients by 2030 and more than 640 million people by 2040. HbA1c value represents average blood glucose over the past 2-3 months and accounts for both pre-prandial and post-prandial blood glucose levels. A link between HbA1c and diabetic complications has been confirmed. In general, patients with controlled diabetes mellitus should have at least biannual testing, while patients with uncontrolled diabetes mellitus or unmet glycemic targets should be tested every three months. The objective was to see compliance of checking HbA1c in tertiary care hospital of a developing world. METHODS: This was a retrospective observational study done from 1st February 2019 to 31st March 2019 in the Department of Medicine and Surgery, The Aga Khan University Hospital, Karachi. All patients of age 18 years and above, admitted with a diagnosis of diabetes mellitus (DM)from 1st February 2019 to 31st March 2019 were included. If HbA1c was less than 7% the patients were labelled as having controlled DM, otherwise, uncontrolled DM. If HbA1c of patients with controlled DM was not checked in last six months and if HbA1c of patients with uncontrolled DM was not checked in last three months then it was labelled as non-compliance of checking HbA1c. RESULTS: Out of 1732 diabetic patients only 94 patients fulfilled inclusion criteria. Out of these 94 patients 43 (45.7%) were male. Mean HbA1c was 7.90% (1.4) and 69 (73.4%) patients had uncontrolled diabetes mellitus. Overall, the compliance of checking HbA1c was 58.5%. In uncontrolled diabetes mellitus patients, the compliance of checking HbA1c was 45% and in controlled diabetes mellitus patients the compliance was 96%. CONCLUSION: The compliance of checking HbA1c is inadequate in diabetic inpatients. The considerable prevalence of diabetes and the benefits of timely interventions in diagnosed patients to prevent complications suggest the need for a comprehensive awareness among the doctors for checking HbA1c.

SHORT COMMUNICATION-Inappropriate use of proton pump inhibitor for stress ulcer prophylaxis in a tertiary care hospital in Karachi, Pakistan.

The use of proton pump inhibitors (PPI) has been expanded inappropriately. PPI are among the most selling drugs in the world. There is growing evidence that PPI are associated with significant adverse effects along with undue financial burden. Inappropriate prescription of PPI is common in inpatients. The objective is to determine the frequency of inappropriate use of proton pump inhibitors for stress ulcer prophylaxis. This prospective observational study was conducted in the Department of Medicine of The Aga Khan University Hospital Karachi. 151 adult patients admitted in the hospital were included. All those patients who received PPI due to a condition mentioned by American Gastroenterology Association (AGA) as an indication for PPI, were labeled as PPI appropriately indicated. While those patients who received PPI without a condition mentioned by AGA as an indication for PPI, were labeled as PPI inappropriately indicated. Mean age was 57.2±18.2 years. Route of administration was oral in 110 (72.8%) and IV in 41 (27.2%) patients. Out of 151 patients, 100 (66.2%) patients were receiving PPI without any specific indication while 51 (33.8%) patients were receiving PPI with appropriate indications. Our study showed that inappropriate use of PPI is quite common among admitted patients.

Ratings of performance in multisource feedback: comparing performance theories of residents and nurses.

BACKGROUND: Multisource feedback (MSF) is increasingly being used to assess trainee performance, with different assessor groups fulfilling a crucial role in utility of assessment data. However, in health professions education, research on assessor behaviors in MSF is limited. When assessing trainee performance in work settings, assessors use multidimensional conceptualizations of what constitutes effective performance, also called personal performance theories, to distinguish between various behaviors and sub competencies., This may not only explain assessor variability in Multi Source Feedback, but also result in differing acceptance (and use) of assessment data for developmental purposes. The purpose of this study was to explore performance theories of various assessor groups (residents and nurses) when assessing performance of residents. METHODS: A constructivist, inductive qualitative research approach and semi-structured interviews following MSF were used to explore performance theories of 14 nurses and 15 residents in the department of internal medicine at Aga Khan University (AKU). Inductive thematic content analysis of interview transcripts was used to identify and compare key dimensions in residents' and nurses' performance theories used in evaluation of resident performance. RESULTS: Seven major themes, reflecting key dimensions of assessors' performance theories, emerged from the qualitative data, namely; communication skills, patient care, accessibility, teamwork skills, responsibility, medical knowledge and professional attitude. There were considerable overlaps, but also meaningful differences in the performance theories of residents and the nurses, especially with respect to accessibility, teamwork and medical knowledge. CONCLUSION: Residents' and nurses' performance theories for assessing resident performance overlap to some extent, yet also show meaningful differences with respect to the performance dimensions they pay attention to or consider most important. In MSF, different assessor groups may therefore hold different performance theories, depending on their role. Our results further our understanding of assessor source effects in MSF. Implications of our findings are related to implementation of MSF, design of rating scales as well as interpretation and use of MSF data for selection and performance improvement.

Tumour induced osteomalacia.

Tumour-induced osteomalacia (TIO) is a rare paraneoplastic syndrome usually presenting with bone pain, fracture of bones and muscle weakness. It is caused by high serum levels of fibroblast growth factor 23 (FGF- 23), which is a hormone-regulating phosphate, and vitamin D. FGF-23 is secreted by several tumours, especially benign mesenchymal tumours which are very small and difficult to locate. There is a significant delay from onset of symptoms to the diagnosis of this entity dueto occult nature of this disease. We present a case of young male who presented with long history of progressively worsening muscular pain and weakness, rendering the patient confined to bed. Our aim of presenting this patient as a case report is to make physicians realise that any patient with unexplained muscular weakness and pain must undergo workup for TIO, including serum phosphate measurement, as this is a rare but potentially curable disease.