CD4 trajectory adjusting for dropout among HIV-positive patients receiving combination antiretroviral therapy in an East African HIV care centre

Objective

Estimates of CD4 response to antiretroviral therapy (ART) obtained by averaging data from patients in care, overestimate population CD4 response and treatment program effectiveness because they do not consider data from patients who are deceased or not in care. We use mathematical methods to assess and adjust for this bias based on patient characteristics.

Design

We examined data from 25,261 HIV-positive patients from the East Africa IeDEA Consortium.

Methods

We used inverse probability of censoring weighting (IPCW) to represent patients not in care by patients in care with similar characteristics. We address two questions: What would the median CD4 be “had everyone starting ART remained on observation?” and “were everyone starting ART maintained on treatment?”

Results

Routine CD4 count estimates were higher than adjusted estimates even under the best-case scenario of maintaining all patients on treatment. Two years after starting ART, differences between estimates diverged from 30 cells/µL, assuming similar mortality and treatment access among dropouts as patients in care, to over 100 cells/µL assuming 20% lower survival and 50% lower treatment access among dropouts. When considering only patients in care, the proportion of patients with CD4 above 350 cells/µL was 50% adjusted to below 30% when accounting for patients not in care. One-year mortality diverged 6–14% from the naïve estimates depending on assumptions about access to care among lost patients.

Conclusions

Ignoring mortality and loss to care results in over-estimation of ART response for patients starting treatment and exaggerates the efficacy of treatment programs administering it.     

Effect of terbutaline on peripheral lymph flow, protein concentration and transport, and edema formation after thermal injury in rabbits

In the rabbit, intraarterial infusion of 5 micrograms/min of terbutaline within the first two hours after moderate thermal injury prevents edema and reduces augmented lymph flow, lymphatic protein transport, and tissue fluid protein concentration. Terbutaline, however, fails to prevent edema 4 hours after thermal injury although the increase of leg volume (24%) is less than in the untreated, burned control leg (56%). A higher dose of terbutaline (15 micrograms/min) also fails to block edema 4 hours after burning and its effect on leg volume, lymph flow, and lymphatic protein concentration is similar to that of 5 micrograms/min infusion. Terbutaline does not alter the extent of tissue injury after burning as the increase in tissue fluid lactic dehydrogenase and potassium are similar with "treated" and "untreated" burns.     

Intrarenal dopamine inhibits progression of diabetic nephropathy

The kidney has a local intrarenal dopaminergic system, and in the kidney, dopamine modulates renal hemodynamics, inhibits salt and fluid reabsorption, antagonizes the renin-angiotensin system, and inhibits oxidative stress. The current study examined the effects of alterations in the intrarenal dopaminergic system on kidney structure and function in models of type 1 diabetes. We studied catechol-O-methyl-transferase (COMT)(-/-) mice, which have increased renal dopamine production due to decreased dopamine metabolism, and renal transplantation was used to determine whether the effects seen with COMT deficiency were kidney-specific. To determine the effects of selective inhibition of intrarenal dopamine production, we used mice with proximal tubule deletion of aromatic amino acid decarboxylase (ptAADC(-/-)). Compared with wild-type diabetic mice, COMT(-/-) mice had decreased hyperfiltration, decreased macula densa cyclooxygenase-2 expression, decreased albuminuria, decreased glomerulopathy, and inhibition of expression of markers of inflammation, oxidative stress, and fibrosis. These differences were also seen in diabetic mice with a transplanted kidney from COMT(-/-) mice. In contrast, diabetic ptAADC(-/-) mice had increased nephropathy. Our study demonstrates an important role of the intrarenal dopaminergic system to modulate the development and progression of diabetic kidney injury and indicate that the decreased renal dopamine production may have important consequences in the underlying pathogenesis of diabetic nephropathy.     

Cryopreserved iliac artery allograft for primary arterial revascularization in adult liver transplantation

Arterial allograft represents a material of choice for primary arterial revascularization in liver transplantation (LT) when interposition of a vascular conduit is required. In case of non-availability of such graft, the use of cryopreserved vessels should be an interesting option. Three patients were grafted using a cryopreserved iliac artery allograft (CIAA) previously harvested and stored at -140°C in a tissue bank. An auxiliary partial LT was performed in one patient for acute liver failure. During follow-up, an efficient regeneration of the native hemi-liver was observed while atrophy of the auxiliary graft occurred, leading to functional portal vein and hepatic artery thrombosis at six and nine months, respectively. Two other patients presented with celiac trunk compression because of arcuate ligament without available arterial allograft in the donor. Late arterial thrombosis occurred at six months in one patient without impairment of graft function. The last patient was alive and symptom free 29 months after LT with a patent cryopreserved arterial conduit. Our preliminary results suggest that CIAA might represent an efficient solution as vessel interposition for primary arterial hepatic revascularization in LT setting when no other suitable graft is available. However, long-term patency of CIAA remains questionable.     

Inpatient and 90-day post-discharge outcomes in elective Medicare spine fusion surgery

Background Context

Elective spine surgery is a commonly performed operative procedure, that requires knowledge of risk-adjusted results to improve outcomes and reduce costs.

Anatomy of the lateral antebrachial cutaneous and superficial radial nerves in the forearm: a cadaveric and clinical study

PURPOSE: To define the anatomy of the lateral antebrachial cutaneous nerve (LACN) and the superficial radial nerve (SRN) in relation to easily identifiable landmarks in the dorsoradial forearm to minimize the risk to both nerves during surgical approaches to the dorsal radius. METHODS: In this study 37 cadaveric forearms and 20 patients having distal radius external fixation were dissected to identify these nerves in relation to various anatomic landmarks. RESULTS: Based on these dissections the anatomy was divided into 2 zones that can be identified by easily visible and palpable landmarks. Zone 1 extends from the elbow to the cross-over of the abductor pollicis longus with the extensor carpi radialis brevis and longus. Zone 2 is distal to the cross-over. In zone 1 the 2 nerves can be differentiated through limited incisions based on their depth and anatomic location. Within this zone the SRN is deep to the brachioradialis until 1.8 cm proximal to zone 2 (9 cm proximal to the radial styloid), where it becomes superficial and pierces the fascia of the mobile wad and then remains deep to the subcutaneous fat. In contrast the LACN pierces the fascia between the brachialis and biceps muscles at the level of the elbow. In all specimens the LACN ran parallel to the cephalic vein within the subcutaneous fat. In 31 specimens it ran volar to the vein and in 5 specimens the nerve crossed under the cephalic vein at the elbow and ran dorsal to the vein in the forearm. One specimen had 2 branches with 1 on either side of the vein. Differentiation of these nerves was found to be possible through limited incisions in zone 1 during placement of external fixation pins for distal radius fractures. The LACN always was located in the superficial fat running with the cephalic vein, whereas the SRN was deeper to this nerve either covered by the brachioradialis or closely adherent to it within the investing fascia of the mobile wad. In zone 2 the nerves arborized and ran in the same tissue plane, making differentiation through limited incisions difficult. CONCLUSIONS: Dividing forearm anatomy into zones aids in understanding the complex 3-dimensional anatomy. Recognition of the consistent location of both the LACN and SRN facilitates surgical exposure. This allows localization through limited incisions during nerve repair and hardware placement, thereby enhancing uncomplicated and favorable outcomes.     

Self-reported hypoglycaemia in insulin-treated patients with diabetes mellitus: results from the Singapore cohort of the International Operations Hypoglycaemia Assessment Tool study

INTRODUCTIONHypoglycaemia constitutes a significant barrier to achieving glycaemic control with insulin in both Type 1 (T1DM) and Type 2 diabetes mellitus (T2DM). The International Operations Hypoglycaemia Assessment Tool (IO HAT) study was designed to determine the incidence of hypoglycaemia in insulin-treated patients with T1DM and T2DM.METHODSThe IO HAT study retrospectively and prospectively assessed the incidence of hypoglycaemia in patients with insulin-treated diabetes mellitus in nine countries. This sub-analysis included patients from Singapore with T1DM or T2DM who were aged ≥ 21 years and had completed two self-assessment questionnaires (SAQ1 and SAQ2).RESULTSOf the 50 T1DM and 320 T2DM patients who completed the SAQ1, 39 T1DM and 265 T2DM patients completed SAQ2; 100% and 90.9%, respectively, experienced at least one hypoglycaemic event prospectively. The incidence rates of any hypoglycaemia were 49.5 events per patient-year (EPPY) and 16.1 EPPY for T1DM and T2DM patients, respectively, in the four-week prospective period. Hypoglycaemia rate did not differ in terms of glycated haemoglobin level. The vast majority of T1DM or T2DM patients (92.0% and 90.7%, respectively) knew the overall definition of hypoglycaemia before study participation, although over half of the patients (T1DM 54.0%, T2DM 51.9%) defined hypoglycaemia based only on symptoms.CONCLUSIONHigh proportions of insulin-treated patients with diabetes mellitus in Singapore reported hypoglycaemic events prospectively, showing that they had underreported hypoglycaemic episodes retrospectively. Patient education can help in improving hypoglycaemia awareness and its management in the region.     

Heart rate variability before the onset of ventricular tachycardia: differences between slow and fast arrhythmias

BACKGROUND: We tested whether or not heart rate variability (HRV) changes can serve as early signs of ventricular tachycardia (VT) and predict slow and fast VT in patients with an implantable cardioverter defibrillator (ICD). METHODS AND RESULTS: We studied the ICD stored 1000 beat-to-beat intervals before the onset of VT (131 episodes) and during a control time without VT (74 series) in 63 chronic heart failure ICD patients. Standard HRV parameters as well as two nonlinear parameters, namely 'Polvar10' from symbolic dynamics and the finite time growth rates 'Fitgra9' were calculated. Comparing the control and the VT series, no linear HRV parameter showed a significant difference. The nonlinear parameters detected a significant increase in short phases with low variability before the onset of VT (for time series with less than 10% ectopy, P<0.05). Subdividing VT into fast (cycle length 270 ms) events, we found that the onset of slow VT was characterized by a significant increase in heart rate, whereas fast VT was triggered during decreased heart rates, compared to the control series. CONCLUSIONS: Our data may permit the development of automatic ICD algorithms based on nonlinear dynamic HRV parameters to predict VT before it starts. Furthermore, they may facilitate improved prevention strategies.     

Calcium-sensing receptor autoantibodies are relevant markers of acquired hypoparathyroidism

We investigated the presence of autoantibodies (aAbs) directed against the parathyroid gland in 17 patients with spontaneous isolated acquired hypoparathyroidism. Fourteen patients with acquired hypoparathyroidism (AH) associated with type I or II autoimmune polyendocrinopathy syndrome were also tested in comparison with a control group of 68 subjects without AH, including patients with other autoimmune diseases and healthy blood donors. aAbs against parathyroid tissue were screened using an indirect immunofluorescence technique on primate parathyroid tissue and human parathyroid adenoma. aAbs against the calcium-sensing receptor (CaSR) were analyzed using an immunoblotting assay with the recombinant extracellular domain of the human CaSR as antigen. Seven of the 31 patients with AH were positive for CaSR aAbs. Five of the positive sera were obtained from the group with isolated AH. The two other positive sera were from patients with autoimmune polyendocrinopathy syndrome. The sensitivity of the immunoblotting technique was higher than that of both the radioimmunological test using the extracellular domain of the CaSR and the indirect immunofluorescence technique. There were no positive sera in the control group. In conclusion, using an immunoblotting assay, we demonstrate the presence of CaSR aAbs in about one third of the patients with isolated AH, pointing out the value of detecting such aAbs to assess the autoimmune origin of the disease.