Visceral leishmaniasis (VL) is endemic in Asia, East and North Africa, South America, and Southern Europe, and is a major public health problem in the Indian subcontinent. Miltefosine received approval in 2002 to treat VL in India, and the Indian National Vector Borne Disease Control Programme later adopted a single dose (10 mg/kg) of liposomal amphotericin B. We report results of a randomized trial comparing the efficacy of combination therapy with an Indian preparation of liposomal amphotericin B (single dose of 7.5 mg/kg) and short-course miltefosine (2.5 mg/kg/day for 14 days; n = 66) in comparison to miltefosine monotherapy (2.5 mg/kg/day for 28 days; n = 78). Nine patients in the miltefosine group and three in the combination therapy group had to discontinue therapy because of serious adverse events. At the end of the therapy, the clinical and parasitological cure rate was 100% in both groups. By per-protocol analysis, by 6 months after completion of treatment, 12 of 69 patients in the miltefosine monotherapy arm (17.4%, 95% CI: 10.24–28%) and none in the combination therapy arm had relapse. Over 5 years of follow-up, 10 patients in the miltefosine monotherapy arm (all within 0.5–2 years after completing therapy) and none in the combination therapy arm experienced post–kala-azar dermal leishmaniasis. Combination therapy offered benefits over miltefosine monotherapy for VL in India.

Chloroquine has been the treatment of choice for acute vivax malaria for more than 60 years. Malaria caused by Plasmodium vivax has recently shown resistance to chloroquine in some places. This study compared the efficacy and safety of fixed dose combination (FDC) of arterolane maleate and piperaquine phosphate (PQP) with chloroquine in the treatment of uncomplicated vivax malaria. Patients aged 13–65 years with confirmed mono-infection of P. vivax along with fever or fever in the previous 48 h were included. The 317 eligible patients were randomly assigned to receive FDC of arterolane maleate and PQP (n = 159) or chloroquine (n = 158) for 3 days. Primaquine was given as an anti-relapse measure on day 3 and continued for 14 consecutive days. Primary efficacy analysis included assessment of the proportion of aparasitaemic and afebrile patients at 72 h. Safety endpoints were analysis of adverse events, vital signs, laboratory data, and abnormalities on electrocardiograph. Patients participated in the study for at least 42 days. In per protocol population, the proportion of aparasitaemic and afebrile patients at 72 h was 100 % (140/140) in the FDC of arterolane maleate and PQP group, and 99.3 % (145/146) in the chloroquine group (Fisher, p > 0.9999). In intent to treat population, the corresponding value was reported to be 96.9 % (154/159) in the FDC of arterolane maleate and PQP group and 98.7 % (156/158) in the chloroquine group (Fisher, p = 0.4479). The median parasite clearance time was 24 h in FDC of arterolane maleate and PQP group and 26 h in chloroquine group (Log-rank, p = 0.2264). Similarly, median fever clearance time was 24 h in both the groups (Log-rank, p = 0.7750). In PP population, day 28 cure rates were 100 % in both the groups (95 % CI (96.52, 100.0 for FDC of arterolane maleate and PQP and 96.73, 100.0 in chloroquine group)). Incidence of adverse events was 82.4 % in the FDC of arterolane maleate and PQP group and 85.4 % in the chloroquine group. Most of the adverse events were mild to moderate in intensity. The commonly reported clinical adverse events in the FDC of arterolane maleate and PQP versus chloroquine group were vomiting (5.0 vs 5.1 %), headache (1.3 vs 3.2 %) and prolonged QT (1.9 vs 3.2 %). No deaths were reported. The pharmacokinetic analysis indicates that arterolane maleate is well absorbed and has a relatively short t1/2 of 3.2 h. Piperaquine is also well absorbed after oral administration with a t1/2 of about 228.33 h. The study showed that FDC of arterolane maleate and PQP effectively cured vivax malaria and attained acceptable level of cure up to day 28. Both the groups showed similar safety profile. Trial Registration Clinical Trial Registry India: CTRI/2011/11/002129

We assessed the association between polypharmacy and cardiovascular autonomic function among community-dwelling elderly patients having chronic diseases. Three hundred and twenty-one patients from an urban municipality area of Kolkata, India were studied in August 2022. The anticholinergic burden and cardiac autonomic function (Valsalva ratio, orthostatic hypotension, change in diastolic blood pressure after an isometric exercise, and heart rate variability during expiration and inspiration) were evaluated. Binary logistic regression analysis was performed to find out the association of polypharmacy and total anticholinergic burden with cardiac autonomic neuropathy. A total of 305 patients (age, 68.9 ± 3.4; 65.9% male) were included. Of these patients, 81 (26.6%) were on polypharmacy. Out of these 81 patients, 42 patients were on ninety-eight potential inappropriate medications. The anticholinergic burden and the proportion of patients with cardiac autonomic neuropathy were significantly higher among patients who were on polypharmacy than those who were not (8.1 ± 2.3 vs. 2.3 ± 0.9; p = 0.03 and 56.8% vs. 44.6%; p = 0.01). The presence of polypharmacy and a total anticholinergic burden of > 3 was significantly associated with cardiac autonomic neuropathy (aOR, 2.66; 95% CI, 0.91–3.98 and aOR, 2.51; 95% CI, 0.99–3.52, respectively). Thus, polypharmacy was significantly associated with cardiac autonomic neuropathy among community-dwelling elderly patients.

Clinical Pharmacologists play a major role in facilitating the rational use of medicines.^[1] The World Health Organization insists on integrating the Clinical Pharmacology discipline with the health service system^[2]; however, there is procrastination in materializing this.^[3] We describe ten instances wherein Clinical Pharmacological interventions improved prescribing and patient outcomes ( Table 1). ... ... Clinical Pharmacologists and clinical pharmacists promote the safer and effective use of medicines.^[13] Their consultations should be encouraged to improve treatment outcomes. No funding was obtained for this work. The authors have no relevant financial or non-financial interests to disclose. The idea for drafting this article was conceptualised by SD, SSS, and SKT. The patients described in this article were treated and consulted by SD, SSS, S. Sarkar, S. Sen, S. Selvarajan, SKT, JP, NC, and SRJ. The literature search was performed by SD and SM. Expert inputs were provided by AP, CSL, S. Selvarajan, and SKT. All authors contributed to the writing and proofreading of the final manuscript. The final manuscript was discussed and approved by all authors.