Receiving healthcare for drug-resistant TB: a cross-sectional survey from Pakistan

OBJECTIVE:To describe and quantify patients’ self-reported experiences of receiving healthcare from Pakistan’s Programmatic Management of Drug-Resistant Tuberculosis (PMDT) model of care, and to understand these experiences within the broader context of Pakistan’s health system.METHOD:This was a cross-sectional survey of patients attending three PMDT clinics in Khyber-Pakhtunkhwa Province in Pakistan.RESULTS:The median consultation time at the PMDT clinics was 10 minutes. In their most recent visit to the PMDT clinic, 34.9% of patients spent >40% of their monthly income to access treatment. To specify, 71% of patients reported spending out-of-pocket for ancillary medicines and 44.7% for laboratory tests. In 10.5% of cases, medicines for drug-resistant TB (DR-TB) were dispensed without the patient attending the clinic. Only 43.7% of treatment supporters regularly accompanied patients to the clinic, and 6% supervised the patient’s intake of medicines. Disbursement of financial support was irregular in 98.6% of cases. Only 6.2% of patients received their daily injections from a public facility, the rest went elsewhere.CONCLUSION:Several shortcomings in PMDT services, including hurried consultations, irregularities in financial support, and gaps in Pakistan’s broader health system undermined healthcare experience of patients with DR-TB. To improve health outcomes and patients’ care experience these service gaps need to be addressed.     

Cardiovascular magnetic resonance in patients with pectus excavatum compared with normal controls

Purpose

To assess cardiothoracic structure and function in patients with pectus excavatum compared with control subjects using cardiovascular magnetic resonance imaging (CMR).

Method

Thirty patients with pectus excavatum deformity (23 men, 7 women, age range: 14-67 years) underwent CMR using 1.5-Tesla scanner (Siemens) and were compared to 25 healthy controls (18 men, 7 women, age range 18-50 years). The CMR protocol included cardiac cine images, pulmonary artery flow quantification, time resolved 3D contrast enhanced MR angiography (CEMRA) and high spatial resolution CEMRA. Chest wall indices including maximum transverse diameter, pectus index (PI), and chest-flatness were measured in all subjects. Left and right ventricular ejection fractions (LVEF, RVEF), ventricular long and short dimensions (LD, SD), mid-ventricle myocardial shortening, pulmonary-systemic circulation time, and pulmonary artery flow were quantified.

Results

In patients with pectus excavatum, the pectus index was 9.3 ± 5.0 versus 2.8 ± 0.4 in controls (P < 0.001). No significant differences between pectus excavatum patients and controls were found in LV ejection fraction, LV myocardial shortening, pulmonary-systemic circulation time or pulmonary flow indices. In pectus excavatum, resting RV ejection fraction was reduced (53.9 ± 9.6 versus 60.5 ± 9.5; P = 0.013), RVSD was reduced (P < 0.05) both at end diastole and systole, RVLD was increased at end diastole (P < 0.05) reflecting geometric distortion of the RV due to sternal compression.

Conclusion

Depression of the sternum in pectus excavatum patients distorts RV geometry. Resting RVEF was reduced by 6% of the control value, suggesting that these geometrical changes may influence myocardial performance. Resting LV function, pulmonary circulation times and pulmonary vascular anatomy and perfusion indices were no different to controls.     

Changes in Auditory Nerve Responses Across the Duration of Sinusoidally Amplitude-Modulated Electric Pulse-Train Stimuli

Response rates of auditory nerve fibers (ANFs) to electric pulse trains change over time, reflecting substantial spike-rate adaptation that depends on stimulus parameters. We hypothesize that adaptation affects the representation of amplitude-modulated pulse trains used by cochlear prostheses to transmit speech information to the auditory system. We recorded cat ANF responses to sinusoidally amplitude-modulated (SAM) trains with 5,000 pulse/s carriers. Stimuli delivered by a monopolar intracochlear electrode had fixed modulation frequency (100 Hz) and depth (10%). ANF responses were assessed by spike-rate measures, while representation of modulation was evaluated by vector strength (VS) and the fundamental component of the fast Fourier transform (F₀ amplitude). These measures were assessed across the 400 ms duration of pulse-train stimuli, a duration relevant to speech stimuli. Different stimulus levels were explored and responses were categorized into four spike-rate groups to assess level effects across ANFs. The temporal pattern of rate adaptation to modulated trains was similar to that of unmodulated trains, but with less rate adaptation. VS to the modulator increased over time and tended to saturate at lower spike rates, while F₀ amplitude typically decreased over time for low driven rates and increased for higher driven rates. VS at moderate and high spike rates and degree of F₀ amplitude temporal changes at low and moderate spike rates were positively correlated with the degree of rate adaptation. Thus, high-rate carriers will modify the ANF representation of the modulator over time. As the VS and F₀ measures were sensitive to adaptation-related changes over different spike-rate ranges, there is value in assessing both measures.     

Response Properties of the Refractory Auditory Nerve Fiber

The refractory characteristics of auditory nerve fibers limit their ability to accurately encode temporal information. Therefore, they are relevant to the design of cochlear prostheses. It is also possible that the refractory property could be exploited by prosthetic devices to improve information transfer, as refractoriness may enhance the nerve's stochastic properties. Furthermore, refractory data are needed for the development of accurate computational models of auditory nerve fibers. We applied a two-pulse forward-masking paradigm to a feline model of the human auditory nerve to assess refractory properties of single fibers. Each fiber was driven to refractoriness by a single (masker) current pulse delivered intracochlearly. Properties of firing efficiency, latency, jitter, spike amplitude, and relative spread (a measure of dynamic range and stochasticity) were examined by exciting fibers with a second (probe) pulse and systematically varying the masker-probe interval (MPI). Responses to monophasic cathodic current pulses were analyzed. We estimated the mean absolute refractory period to be about 330 micros and the mean recovery time constant to be about 410 micros. A significant proportion of fibers (13 of 34) responded to the probe pulse with MPIs as short as 500 micros. Spike amplitude decreased with decreasing MPI, a finding relevant to the development of computational nerve-fiber models, interpretation of gross evoked potentials, and models of more central neural processing. A small mean decrement in spike jitter was noted at small MPI values. Some trends (such as spike latency-vs-MPI) varied across fibers, suggesting that sites of excitation varied across fibers. Relative spread was found to increase with decreasing MPI values, providing direct evidence that stochastic properties of fibers are altered under conditions of refractoriness.     

Bone debridement and limb lengthening in type III open tibial shaft fractures: No infection or nonunion in 9 patients

We retrospectively reviewed a consecutive series of 9 patients with tibial shaft fractures and extensive soft tissue damage, who had completed treatment by means of bone resection and distraction. 4 patients had type IIIB fractures and 5 type IIIC. The median follow-up time after bone resection was 27 (12-43) months. All patients were treated with debridement of devitalized soft tissue and resection of dead bone at the fracture site. The median bone shortening was 4 (3-9) cm. Equal limb-length was restored by proximal corticotomy and lengthening. A free vascular flap in 5 patients and a local flap in 4 patients corrected the soft tissue loss. All soft tissue transfers were successful, except in 1 case, which healed after a new free flap was made. The median union time of the fracture was 8 (4.5-28) months from the injury and 7 (3-10) months from the time of bone resection. There were no deep infections or nonunions and no secondary amputations.

This series shows that bone debridement and limb lengthening, with a multidisciplinary approach, is often successful in salvaging limbs at high risk of amputation.     

Cholangiocarcinoma in Primary Sclerosing Cholangitis

Introduction

Cholangiocarcinoma (CCA) is an aggressive and nearly always fatal tumor of the biliary tract.

Purpose

This review explores risk factors, epidemiology, current diagnostic approaches, and treatment of CCA arising in patients with primary sclerosing cholangitis (PSC).

Methods

We review latest recommendations about screening strategies to enable the early detection of CCA in PSC, using CA 19-9 and ultrasound imaging, as well as fluorescent in situ hybridization techniques to enhance the accuracy of biliary cytology. We also review the emerging role of liver transplantation.     

Cutaneous sebaceous neoplasms as markers of Muir-Torre syndrome: a diagnostic algorithm

Sebaceous gland neoplasms such as adenoma, epithelioma, and carcinoma are uncommon cutaneous tumors. Although sporadic, their occurrence is clinically significant because of their association with Muir‐Torre syndrome (MTS). MTS is a rare autosomal dominant genodermatosis characterized by the occurrence of sebaceous gland neoplasms and/or keratoacanthomas associated with visceral malignancies that include gastrointestinal and genitourinary cancers. MTS is usually the result of germline mutation in one or more of the DNA mismatch repair (MMR) genes. MMR genes commonly implicated include MSH‐2 and MLH‐1 and, more recently, MSH‐6. Recent evidence suggests that immunohistochemistry is very sensitive and effective in detecting these defects in cutaneous tumors in MTS. In addition, the genetic instability of cutaneous and visceral tumors in MTS caused by the defects in MMR genes can also be detected, using polymerase chain reaction (PCR)‐based techniques, for microsatellite instability (MSI). Given that some sebaceous neoplasms represent cutaneous markers of MTS, what should we as dermatopathologists be advocating? Should we be looking for absence/loss of MMRs in all sebaceous neoplasms? When should we recommend assaying for MSI? This review attempts to address all of these issues with a view to streamlining the work‐up of a patient presenting for the first time with a sebaceous neoplasm and no prior personal or family history of internal malignancies.