1) A clinical trial evaluated the efficacy and safety of a 24-week, all-oral regimen for treating rifampin-resistant tuberculosis compared to the standard 9-20 month treatment regimen. 2) The 24-week regimen was found to be non-inferior and had better safety outcomes than the standard regimen, with 11% of patients experiencing treatment failure or other adverse events compared to 48% in the standard group. 3) A separate clinical trial evaluated the iron chelator deferiprone for treating early-stage Parkinson's disease and found that while it reduced brain iron levels, patients receiving deferiprone experienced worse motor and non-motor symptoms and required dopaminergic therapy more often than the placebo group

2. JOURNAL CLUB
PRESENTATION BY:
DR. MUAZZAM ALI
PGR WEST MEDICAL WARD

3. IMAGE CHALLENGE

4. Zubaida Bibi 51 Year old female normotensive
Hyperglycemic presented in ER with H/O SOB grade 3
gradual in onset (progressive from grade 2 to 3) from 1 day.

6. • Chest Xray PA View
• Rotation Normal
• Trachea Central
• Bones Normal
• Cardiothoracic Ratio >0.5
• Costophrenic and Cardiophrenic Angles Obliterated on Both
sides.
• There are multiple Variable size Soft tissue Attenuation
nodules Noted scattered throughout Both lung fields.There is
Loss of silhouetting of right heart border.
• Features likely suggestive of Pulmonary mets.

7. Diagnosis
• Metastatic Lesions

8. • Sajid Hussain 33 years old male normotensive
normoglycemic K/C of MVR since 2015 presented in ER
with H/O ASOC from 2 days gradual onset associated
with vomiting headache.There is H/O fever from 1.5
months high grade intermittent associated with rigors
and chills.His CT Brain plain shows

10. • C.T Scan without contrast
• Axial view
• Slight effacement of gyri and sulci
• Multiple variable sized brain cavities are noted in Left
high parietal Right basal ganglia Right occipital Lobe and
Left temporo-Occipital
• No midline shift
• Rest of visualized Brain parenchyma appears normal.

11. Differential Diagnosis
1-Toxoplasmosis
2-Lymphoma
3-Metastasis

13. • M Razzaq 55 years old male with no Diabatic
Hypertensive presented to E/R with severe central chest
pain from 2 hours radiating to Left arm and Jaw
associated with vomiting 2 episodes and profused
sweating.His ECG shows

15. • 12 Lead ECG
• HR 50 beats/min Approx
• Axis NORMAL
• ST Segment elevation in leads 2,3 and AvF and Right sided
lead v4 with Reciprocal ST segment depressions in leads 1 and
AvL

16. Complications of MI

17. A 24-Week, All-Oral Regimen for Rifampin-
Resistant Tuberculosis
ABSTRACT
BACKGROUND
• In patients with rifampin-resistant tuberculosis,
all-oral treatment regimens that are more
effective, shorter, and have a more acceptable
side-effect profile than current regimens are
needed.

18. • METHODS
• We conducted an open-label, phase 2–3, multicenter,
randomized, controlled, noninferiority trial to evaluate the
efficacy and safety of three 24-week, all-oral regimens for the
treatment of rifampin-resistant tuberculosis. Patients in
Belarus, South Africa, and Uzbekistan who were 15 years of
age or older and had rifampin-resistant pulmonary
tuberculosis were enrolled. In stage 2 of the trial, a 24-week
regimen of bedaquiline, pretomanid, linezolid, and
moxifloxacin (BPaLM) was compared with a 9-to-20-month
standard-care regimen. The primary outcome was an
unfavorable status (a composite of death, treatment failure,
treatment discontinuation, loss to follow-up, or recurrence of
tuberculosis) at 72 weeks after randomization. The
noninferiority margin was 12 percentage points.

19. • RESULTS
Recruitment was terminated early. Of 301 patients
in stage 2 of the trial, 145, 128, and 90 patients
were evaluable in the intention-to-treat, modified
intention-to-treat, and per-protocol populations,
respectively. In the modified intention-to-treat
analysis, 11% of the patients in the BPaLM group
and 48% of those in the standard-care group had a
primary-outcome event (risk difference, −37
percentage points; 96.6% confidence interval [CI],
−53 to −22).

20. In the per-protocol analysis, 4% of the
patients in the BPaLM group and 12% of
those in the standard-care group had a
primary-outcome event (risk difference, −9
percentage points; 96.6% CI, −22 to 4). In the
as-treated population, the incidence of
adverse events of grade 3 or higher or serious
adverse events was lower in the BPaLM
group than in the standard-care group (19%
vs. 59%).

21. • CONCLUSIONS
• In patients with rifampin-resistant pulmonary
tuberculosis, a 24-week, all-oral regimen was
noninferior to the accepted standard-care
treatment, and it had a better safety profile.

22. Trial of Deferiprone in Parkinson’s
Disease
ABSTRACT
BACKGROUND
Iron content is increased in the substantia nigra of
persons with Parkinson’s disease and may
contribute to the pathophysiology of the disorder.
Early research suggests that the iron chelator
deferiprone can reduce nigrostriatal iron content in
persons with Parkinson’s disease, but its effects on
disease progression are unclear.

23. METHODS
We conducted a multicenter, phase 2,
randomized, double-blind trial involving
participants with newly diagnosed Parkinson’s
disease who had never received levodopa.
Participants were assigned (in a 1:1 ratio) to
receive oral deferiprone at a dose of 15 mg per
kilogram of body weight twice daily or matched
placebo for 36 weeks. Dopaminergic therapy was
withheld unless deemed necessary for symptom
control.

24. The primary outcome was the change in the total
score on the Movement Disorder Society–
sponsored revision of the Unified Parkinson’s
Disease Rating Scale (MDS-UPDRS; range, 0 to
260, with higher scores indicating more severe
impairment) at 36 weeks. Secondary and
exploratory clinical outcomes at up to 40 weeks
included measures of motor and nonmotor
disability. Brain iron content measured with the use
of magnetic resonance imaging was also an
exploratory outcome.

25. RESULTS
A total of 372 participants were enrolled; 186 were
assigned to receive deferiprone and 186 to receive
placebo. Progression of symptoms led to the initiation
of dopaminergic therapy in 22.0% of the participants in
the deferiprone group and 2.7% of those in the
placebo group. The mean MDS-UPDRS total score at
baseline was 34.3 in the deferiprone group and 33.2 in
the placebo group and increased (worsened) by 15.6
points and 6.3 points, respectively (difference, 9.3
points; 95% confidence interval, 6.3 to 12.2; P<0.001).

26. Nigrostriatal iron content decreased more in the
deferiprone group than in the placebo group.
The main serious adverse events with
deferiprone were agranulocytosis in 2
participants and neutropenia in 3 participants.

27. CONCLUSIONS
In participants with early Parkinson’s disease
who had never received levodopa and in whom
treatment with dopaminergic medications was
not planned, deferiprone was associated with
worse scores in measures of parkinsonism
than those with placebo over a period of 36
weeks.